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

OBJECTIVE: 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. METHODS: Case children (n = 50) without cerebral palsy were matched with 43 controls for age, sex, and socioeconomic status. Children underwent T1-weighted (T1w), diffusion-weighted image (DWI) brain MRI and cognitive, behavioural, and motor skills assessment. Stepwise multivariable logistic regression assessed associations between unsuccessful MRI and comprehension (including Weschler Intelligence Scale for Children (WISC-IV) verbal comprehension, working memory, processing speed and full-scale IQ), co-ordination (including Movement Assessment Battery for Children (MABC-2) balance, manual dexterity, aiming and catching, and total scores) and hyperactivity (including Strengths and Difficulties Questionnaire (SDQ) hyperactivity and total difficulties scores). RESULTS: Cases had lower odds of completing both T1w and DWIs (OR: 0.31, 95% CI 0.11-0.89). After adjusting for case-status and sex, lower MABC-2 balance score predicted unsuccessful T1w MRI (OR: 0.81, 95% CI 0.67-0.97, p = 0.022). Processing speed was negatively correlated with relative motion on DWI (r = -0.25, p = 0.026) and SDQ total difficulties score was lower for children with successful MRIs (p = 0.049). CONCLUSIONS: Motion artefacts on brain MRI in early school-age children are related to the developmental profile. IMPACT: Children who had moderate/severe neonatal encephalopathy are less likely to have successful MRI scans than matched controls. Motion artefact on MRI is associated with lower MABC-2 balance scores in both children who received therapeutic hypothermia for neonatal encephalopathy and matched controls, after controlling for case-status and sex. Exclusion of children with motion artefacts on brain MRI can introduce sampling bias, which impacts the utility of neuroimaging to understand the brain-behaviour relationship in children with functional impairments.

Vision function in children 10 years after grade 3 or 4 intraventricular haemorrhage with ventricular dilation: A masked prospective study.

AIM: We examined children 10 to 11 years after grade 3 or 4 intraventricular haemorrhage and ventricular dilation (IVHVD) and investigated whether the grade of IVHVD affected their visual outcome. We explored associations between visual outcomes with cognitive outcomes and extra support at school. METHOD: The visual examinations were part of a 10-year follow-up study for children in a randomized trial. Testers followed a protocol and were masked to whether the child had experienced grade 3 or grade 4 IVHVD and all other data. RESULTS: Thirty-two children were tested: 24 were male and mean (standard deviation) age was 10 years 5 months (1 year 2 months); range 8 years 9 months to 12 years 9 months. All had at least one visual impairment. The median (interquartile range) number of impairments per child was six (six to nine) for children who experienced a grade 4 IVHVD compared with three (two to four) for children who experienced a grade 3 IVHVD (p = 0.003). Each extra vision impairment per child was associated with increased educational support at school, after adjustment for developmental age equivalence (odds ratio = 1.7 [95% confidence interval 1.1-2.6], p = 0.015). INTERPRETATION: Children who experience grade 3 or 4 IVHVD have a high level of visual morbidity at age 10 to 11 years. These children may have unmet visual needs and their outcomes might improve if these needs could be addressed. WHAT THIS PAPER ADDS: Parent-reported questionnaire responses underestimated directly assessed visual morbidity. Grade 4 intraventricular haemorrhage and ventricular dilatation (IVHVD) was followed by more vision impairments than grade 3 IVHVD. Simple tests of visual perceptual skills correlated with the neuropsychology tests. Children with supranuclear eye movement disorders were more likely to be receiving extra help at school. Each additional visual impairment increased the likelihood of extra educational support.

Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.

AIM: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome. METHOD: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2). RESULTS: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013). INTERPRETATION: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.

Mammillary body abnormalities and cognitive outcomes in children cooled for neonatal encephalopathy.

AIM: To evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix. METHOD: Mammillary body abnormalities were scored from T1-weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months-7 years 7 months] and 7 years 4 months [6 years 7 months-7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1-weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion-weighted MRI using deterministic tractography. RESULTS: More cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full-scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities. INTERPRETATION: Cooled children with mammillary body abnormalities at school-age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls. WHAT THIS PAPER ADDS: Cooled children are at higher risk of mammillary body abnormalities than controls. Abnormal mammillary bodies are associated with reduced cognitive scores and smaller hippocampi. Abnormal mammillary bodies are associated with altered mammillothalamic tract diffusivity.

Early intervention programmes for infants at high risk of atypical neurodevelopmental outcome.

The purpose of this review is to present a new framework, EI SMART (early intervention: sensorimotor development, attention and regulation, relationships, and therapist support) for identifying key components that could contribute to more effective interventions for infants at high risk of atypical neurodevelopmental outcome. We present a clinical consensus of current challenges and themes in early intervention, based on multidisciplinary group discussions, including parents of high-risk infants, supported by a literature review. Components to include in early intervention programmes are: (1) promotion of self-initiated, developmentally appropriate motor activity; (2) supporting infant self-regulation and the development of positive parent-infant relationships; and (3) promotion of early communication skills, parent coaching, responsive parenting, and supporting parental mental well-being. Such multimodal programmes may need to be evaluated as a package. WHAT THIS PAPER ADDS: Early intervention programmes should address sensorimotor development, attention, self-regulation, and early communication skills. Therapist input to the programme should include parent coaching and support for parental mental well-being.

PROGRAMAS DE INTERVENCIÓN TEMPRANA PARA LACTANTES CON ALTO RIESGO DE TRATARNOS DEL DESARROLLO NEUROLÓGICO: El propósito de esta revisión es presentar un nuevo marco, EI SMART (intervención temprana: desarrollo sensoriomotor, atención y regulación, relaciones y apoyo del terapeuta) para identificar componentes clave que podrían contribuir a intervenciones más efectivas para los bebés con alto riesgo de desarrollar un trastorno del neurodesarrollo. Presentamos un consenso clínico de los desafíos y temas actuales en la intervención temprana, basados ​​en discusiones grupales multidisciplinares, incluidos los padres de bebés con alto riesgo, respaldados por una revisión de la literatura. Los componentes para incluir en los programas de intervención temprana son (1) la promoción de actividades motoras autoiniciadas y apropiadas para el desarrollo; (2) apoyar la autorregulación infantil y el desarrollo de relaciones positivas entre padres e infantes; (3) promoción de las habilidades de comunicación temprana, entrenamiento de padres, crianza responsable y apoyo al bienestar mental de los padres. Es posible que dichos programas multimodales deban evaluarse como un paquete terapéutico.

PROGRAMAS DE INTERVENÇÃO PRECOCE PARA CRIANÇAS EM ALTO RISCO DE RESULTADO ANORMAL DO DESENVOLVIMENTO: O propósito desta revisão é apresentar um novo formato: EI SMART (intervenção precoce: desenvolvimento sensóriomotor, atenção e regulação, relacionamentos, e apoio do terapeuta) para identificar componentes centrais que podem contribuir para intervenções mais efetivas em lactentes de alto risco. Apresentamos um consenso clínico dos desafios correntes e temas em intervenção precoce, com base em discussões interdisciplinares, incluindo pais de lactentes de alto risco, com apoio de uma revisão de literatura. Os componentes a serem incluídos em programas de intervenção precoce são 1) promoção de atividade motora auto-iniciada apropriada para o desenvolvimento; 2) suporte para a auto-regulação do lactente e desenvolvimento de relações pais-filhos positivas; 3) promoção de habilidades precoces de comunicação, suporte aos pais, parentalidade responsável, e suporte ao bem estar mental dos pais. Tais programas multimodais podem precisar ser avaliados em forma de um pacote.

Attention and visuo-spatial function in children without cerebral palsy who were cooled for neonatal encephalopathy: a case-control study.

Objectives: Dorsal-stream functions are vulnerable to early brain injury associated with neonatal encephalopathy (NE) following perinatal asphyxia, even in children not developing cerebral palsy (CP). Since therapeutic hypothermia (TH) became the standard treatment for NE, the incidence of CP is reduced but the impact on dorsal-stream functions is unknown. We aimed to compare dorsal-stream functions in TH-treated survivors of NE, without CP, with those of matched controls. Methods: We administered tests of dorsal-stream function to 29 case children aged 6-to-8 years treated with TH for NE and without CP, and 20 age, sex and social class matched controls. We used the Conner's Continuous Performance Test (CPT) 2nd Edition to assess attentiveness, based upon Hit Reaction Time (HRT) percentile score and HRT standard error percentile, the CPT HRT block change measure to assess sustained attention and the NEPSY-II block construction and arrows tests to assess visuo-spatial performance and mental rotation. Results: Case children performed significantly worse than controls on measures of attention and visuo-spatial function. Conclusions: Children given TH treatment for NE can have subtle attention difficulties with slower reaction times and reduced visuo-spatial processing. These findings illustrate the continued vulnerability of dorsal-stream functions following NE despite the use of TH.

Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy.

OBJECTIVE: To investigate what proportion of a regional cohort of cooled infants with neonatal encephalopathy develop epilepsy (determined by the International League Against Epilepsy [ILAE] definition and the number of antiepileptic drugs [AEDs]) up to 8 years of age. METHODS: From 2006-2013, 151 infants with perinatal asphyxia underwent 72 h cooling. Clinical and amplitude-integrated electroencepalography (aEEG) with single-channel EEG-verified neonatal seizures were treated with AEDs. Brain magnetic resonance imaging (MRI) was assessed using a 0-11 severity score. Postneonatal seizures, epilepsy rates, and AED treatments were documented. One hundred thirty-four survivors were assessed at 18-24 months; adverse outcome was defined as death or Bayley III composite Cognition/Language or Motor scores <85 and/or severe cerebral palsy or severely reduced vision/hearing. Epilepsy rates in 103 children age 4-8 years were also documented. RESULTS: aEEG confirmed seizures occurred precooling in 77 (57%) 151 of neonates; 48% had seizures during and/or after cooling and received AEDs. Only one infant was discharged on AEDs. At 18-24 months, one third of infants had an adverse outcome including 11% mortality. At 2 years, 8 (6%) infants had an epilepsy diagnosis (ILAE definition), of whom 3 (2%) received AEDs. Of the 103 4- to 8-year-olds, 14 (13%) had developed epilepsy, with 7 (7%) receiving AEDs. Infants/children on AEDs had higher MRI scores than those not on AEDs (median [interquartile range] 9 [8-11] vs. 2 [0-4]) and poorer outcomes. Nine (64%) of 14 children with epilepsy had cerebral palsy compared to 13 (11%) of 120 without epilepsy, and 10 (71%) of 14 children with epilepsy had adverse outcomes versus 23 (19%) of 120 survivors without epilepsy. The number of different AEDs given to control neonatal seizures, aEEG severity precooling, and MRI scores predicted childhood epilepsy. SIGNIFICANCE: We report, in a regional cohort of infants cooled for perinatal asphyxia, 6% with epilepsy at 2 years (2% on AEDs) increasing to 13% (7% on AEDs) at early school age. These AED rates are much lower than those reported in the cooling trials, even with adjusting for our cohort's milder asphyxia. Long-term follow-up is needed to document final epilepsy rates.

Cooling neonates who do not fulfil the standard cooling criteria - short- and long-term outcomes.

AIM: Therapeutic hypothermia is effective and without serious adverse effects in term infants with hypoxic-ischaemic encephalopathy. It is unknown whether other neonatal patient groups could benefit from therapeutic hypothermia. Since 2006, our centre has offered cooling to infants fulfilling the standard cooling criteria, but also to those who did not. METHODS: Observational study with prospective data collection over a 6-year period in a regional cooling centre. Complications and outcome were compared between infants who were cooled not fulfilling the standard inclusion and exclusion criteria as set out in the CoolCap/TOBY protocol (n = 36) and infants who fulfilled the standard entry criteria (n = 129). RESULTS: 21.8% of cooled infants did not fulfil standard cooling entry criteria. This included infants cooled >6 postnatal hours, late preterm infants, and infants with postnatal collapse, major cranial haemorrhage, congenital cardiac disease and surgical conditions. Complication rates and long-term outcome did not differ significantly between the groups, apart from in infants with a major cranial haemorrhage, who had higher rates of coagulopathy and the worst outcome (80% death/disability). CONCLUSION: Cooling can be considered for infants with neonatal encephalopathy following postnatal collapse or preterm birth, those with underlying surgical or cardiac conditions, and infants starting cooling >6 postnatal hours.

Less severe cerebral palsy outcomes in infants treated with therapeutic hypothermia.

AIM: To describe the incidence, type and severity of cerebral palsy at 24 months in a regional cohort of infants treated with whole-body therapeutic hypothermia for neonatal encephalopathy. METHODS: Data were collected prospectively in a regional centre providing TH. Antenatal and perinatal clinical variables and severity of encephalopathy were collected. Infants were assessed at 18 months using the Bayley Scales of Infant and Toddler Development-III, and the presence and severity of CP was investigated at 24 months. RESULTS: A total of 125 of 132 infants fulfilled entry criteria for TH trials and completed 72 h of TH. Sixteen (13%) of the 125 infants died, and eight (6%) were not available for follow-up. Eighteen infants (14%; 18% of those assessed) developed CP. Of these, 12 (67%) were classified using the Gross Motor Function Classification System, at level 1, six (33%) at level 5 and none at levels 2, 3 or 4. CONCLUSION: Our regional clinical cohort had lower mortality and comparable rates of CP compared with historical outcomes in TH trials. In contrast to historical cohorts, only one-third of the 18 children with CP were severely affected and 12 were mildly affected, all of whom were independently ambulant by 24 months.

Neonatal seizures: magnetic resonance imaging adds value in the diagnosis and prediction of neurodisability.

AIM: To determine the aetiological associations, neurological sequelae and role of magnetic resonance imaging (MRI) in term newborn infants with seizures. METHODS: Cohort study of infants ≥37 weeks' gestation delivered in a tertiary level centre, prospectively identified and followed longitudinally for 18-24 months. RESULTS: An underlying aetiology was found in 95% of the 77 infants identified with seizures (3.0/1000 live births). The most common diagnosis was hypoxic-ischaemic encephalopathy (HIE) (65%), followed by neonatal stroke (12%). Nine infants died, 28 of the 68 survivors developed neurodevelopmental impairment (NDI), and 15 had recurrent seizures in the first 2 years, with both outcomes more likely in those with a diagnosis other than HIE. Abnormal MRI findings were found in 45 of the 70 infants imaged. The absence of major cerebral lesions was highly predictive of a normal neurological outcome. CONCLUSION: We report the first cohort of term infants with seizures fully investigated by MRI. The universal use of MRI enabled a cause to be identified in 95% of cases. The probability of having NDI or recurrence of seizures was extremely low with absence of major cerebral lesions on MRI. This study demonstrates the added value of MRI for diagnosis of aetiology and the prediction of neurological outcome.

Factors associated with permanent hearing impairment in infants treated with therapeutic hypothermia.

OBJECTIVE: To define the incidence of hearing impairment, document plasma gentamicin concentrations, and identify factors associated with permanent hearing impairment in infants subjected to therapeutic hypothermia for moderate or severe neonatal encephalopathy. STUDY DESIGN: Data were collected prospectively in a regional center providing therapeutic hypothermia. Cooled infants at ≥ 36 weeks gestation with moderate or severe neonatal encephalopathy were analyzed if a full dataset was available (n = 108), including clinical variables and gentamicin trough levels. Infants with hearing impairment were identified, and survivors were followed up with neurodevelopmental evaluation at age 18 months. Stepwise logistic regression identified factors associated with hearing impairment. RESULTS: Nine infants died, and among the survivors, 10.1% developed a permanent hearing impairment. The trough gentamicin level was above the recommended cutoff of 2 mg/L in 37% of the infants in the entire cohort and in 90% of the infants with hearing impairment. Logistic regression analysis identified high trough gentamicin level, low cord pH, and hypoglycemia (<46.8 mg/dL) in the first postnatal hour as significantly associated with hearing impairment. The need for inotropic support was close to significant (P = .055). CONCLUSION: Hearing impairment was a common finding among cooled infants. Plasma gentamicin levels were commonly >2 mg/L. Based on these findings, we propose changes in gentamicin dosing interval and trough level monitoring to minimize the risk of potentially toxic levels in cooled newborns.

Comparison of Bayley-2 and Bayley-3 scores at 18 months in term infants following neonatal encephalopathy and therapeutic hypothermia.

AIM: Neuroprotection trials for neonatal encephalopathy use moderate or severe disability as an outcome, with the Bayley Scales of Infant Development, Second Edition (Bayley-2) Index scores of <70 as part of the criteria. The Bayley Scales of Infant and Toddler, 3rd Development, Third Edition (Bayley-3) have superseded Bayley-2 and yield higher than expected scores in typically developing and high-risk infants. The aim of this study, therefore, was to compare Bayley-2 scores and Bayley-3 scores in term-born infants surviving neonatal encephalopathy treated with hypothermia. METHOD: Sixty-one term-born infants (37 males, 24 females; median gestational age at birth 40 wks, range 36-42 wks; median birthweight 3280 g, range 2295-5050) following neonatal encephalopathy and hypothermia had contemporaneous assessment at 18 months using the Bayley-2 and Bayley-3. RESULTS: The median Bayley-3 Cognitive Composite score was 7 points higher than the median Bayley-2 Mental Developmental Index (MDI) score and the median Bayley-3 Motor Composite score was 18 points higher than the median Bayley-2 Psychomotor Developmental Index (PDI) score. Ten children had a Bayley-2 MDI of <70; only three children had Bayley-3 combined Cognitive/Language scores of <70. Eleven children had Bayley-2 PDI scores of <70 and four had modified Bayley-3 Motor Composite scores of <70. Applying regression equations to Bayley-3 scores adjusted rates of severe delay to similar proportions found using Bayley-2 scores. INTERPRETATION: Fewer children were classified with severe delay using the Bayley-3 than the Bayley-2, which prohibits direct comparison of scores. Increased Bayley-3 cut-off thresholds for classifying severe disability are recommended when comparing studies in this clinical group using Bayley-2 scores.

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

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.

Development of the corpus callosum and cognition after neonatal encephalopathy.

OBJECTIVE: Neonatal imaging studies report corpus callosum abnormalities after neonatal hypoxic-ischaemic encephalopathy (HIE), but corpus callosum development and relation to cognition in childhood are unknown. Using magnetic resonance imaging (MRI), we examined the relationship between corpus callosum size, microstructure and cognitive and motor outcomes at early school-age children cooled for HIE (cases) without cerebral palsy compared to healthy, matched controls. A secondary aim was to examine the impact of HIE-related neonatal brain injury on corpus callosum size, microstructure and growth. METHODS: Participants aged 6-8 years underwent MRI, the Movement Assessment Battery for Children Second Edition and Wechsler Intelligence Scale for Children Fourth Edition. Cross-sectional area, volume, fractional anisotropy and radial diffusivity of the corpus callosum and five subdivisions were measured. Multivariable regression was used to assess associations between total motor score, full-scale IQ (FSIQ) and imaging metrics. RESULTS: Adjusting for age, sex and intracranial volume, cases (N = 40) compared to controls (N = 39) demonstrated reduced whole corpus callosum area (ß = -26.9, 95% confidence interval [CI] = -53.17, -0.58), volume (ß = -138.5, 95% CI = -267.54, -9.56), fractional anisotropy and increased radial diffusivity (P < 0.05) within segments II-V. In cases, segment V area (ß = 0.18, 95% CI = 0.004, 0.35), volume (ß = 0.04, 95% CI = 0.001, 0.079), whole corpus callosum fractional anisotropy (ß = 13.8 95% CI = 0.6, 27.1) and radial diffusivity (ß = -11.3, 95% CI = -22.22, -0.42) were associated with FSIQ. Growth of the corpus callosum was restricted in cases with a FSIQ ≤85, and volume was reduced in cases with mild neonatal multifocal injury compared to white matter injury alone. INTERPRETATION: Following neonatal HIE, morphological and microstructural changes in the corpus callosum are associated with reduced cognitive function at early school age.

Quality of Life at a 10-Year Follow-Up of Children Born Preterm with Post-Hemorrhagic Ventricular Dilatation: A Cohort Study.

BACKGROUND: Post-haemorrhagic ventricular dilatation (PHVD) is commonly seen in extremely preterm babies, carries significant morbidity, and may cause neonatal mortality. There is a lack of literature on the subsequent health-related quality of life (HRQoL) in childhood. The aim of this work was to assess the quality of life of preterm babies after PHVD at 10 years of age using two validated questionnaires. METHODS: Children with PHVD were assessed as part of the 10-year follow-up of the drainage, irrigation, and fibrinolytic therapy trial. The HRQoL outcome was measured using parent-reported EQ-5D-5L and HUI-3 questionnaires. Both questionnaires produce a summary score anchored at 1 (best health) and 0 (equivalent to death). RESULTS: Median scores at follow-up were 0.65 (IQR 0.36-0.84; n = 44) for the EQ-5D-5L and 0.52 (IQR 0.22-0.87; n = 51) for the HUI-3. Similar proportions had a score below 0.2 (HRQoL [20%], HUI-3 [21%]), while 20% had a HRQoL score above 0.80 compared to 34% using HUI-3. The most severe problems from the EQ-5D-5L were reported in the self-care, mobility, and activity domains, while the HUI-3 reported worse problems in ambulation, cognition, and dexterity domains. Infants with worse (grade 4) intraventricular haemorrhage had poorer HRQoL than those with grade 3 bleeds. CONCLUSION: Children who survive to 10 years of age after PHVD have on average lower HRQoL than their peers. However, the reported range is wide, with a quarter of the children having scores above 0.87 (similar to population norms), while a fifth have very low HRQol scores. Impact was not uniform across domains, with mobility/ambulation a concern across both measures.

Increased inspired oxygen in the first hours of life is associated with adverse outcome in newborns treated for perinatal asphyxia with therapeutic hypothermia.

OBJECTIVE: To assess whether increased inspired oxygen and/or hypocarbia during the first 6 hours of life are associated with adverse outcome at 18 months in term neonates treated with therapeutic hypothermia. STUDY DESIGN: Blood gas values and ventilatory settings were monitored hourly in 61 newborns for 6 hours after birth. We investigated if there was an association between increased inspired oxygen and/or hypocarbia and adverse outcome (death or disability by Bayley Scales of Newborn Development II examination at 18-20 months). RESULTS: Hypothermia was started from 3 hours 45 minutes (10 minutes-10 hours) and median lowest Pco(2) level within the first 6 hours of life was 30 mm Hg (16.5-96 mm Hg). The median highest fraction of inspiratory oxygen within the first hour of life was 0.43 (0.21-1.00). The area under the curve fraction of inspiratory oxygen and Pao(2) for hours 1-6 of life was 0.23 (0.21-1.0) and 86 mm Hg (22-197 mm Hg), respectively. We did not find any association between any measures of hypocapnia and adverse outcome (P > .05), but increased inspired oxygen correlated with adverse outcome, even when excluding newborns with initial oxygenation failure (P < .05). CONCLUSION: Increased fraction of inspired oxygen within the first 6 hours of life was significantly associated with adverse outcome in newborns treated with therapeutic hypothermia following hypoxic ischemic encephalopathy.

Impaired brain growth and neurodevelopment in preterm infants with posthaemorrhagic ventricular dilatation.

AIM: To correlate volumetric magnetic resonance imaging at term with neurodevelopmental outcome at 2 years in infants with posthaemorrhagic ventricular dilatation. Preterm infants with posthaemorrhagic ventricular dilatation have high risk of disabilities, but the range is wide and predicting severity of motor and mental disability is difficult. METHODS: Twenty-five preterm infants with posthaemorrhagic ventricular dilatation had cerebral magnetic resonance imaging at term age. Total and regional brain volumes were calculated using a manual segmentation technique. Bayley Scales of Infant Development II were assessed at 2 years post-term. Developmental Quotients (DQ) were calculated from Developmental Age Equivalent scores. RESULTS: Total cerebral volume, excluding ventricles, correlated positively with Motor (r = 0.7, p < 0.0001) and Mental DQ (r = 0.4, p = 0.02). Only three of 16 infants with cerebral volume <336 cm(3) were ambulant at 2 years. Cerebellar volumes correlated strongly with Motor DQ (r = 0.6, p = 0.002) but only with Mental DQ after adjustment. Thalamic volumes correlated strongly with Motor DQ (r = 0.7, p = 0.0002). CONCLUSION: Brain growth is significantly impaired in posthaemorrhagic ventricular dilatation. Volumetric measurements at term of total cerebral and cerebellar volume may have a role in predicting severity of disability.

Lactate dehydrogenase in hypothermia-treated newborn infants with hypoxic-ischaemic encephalopathy.

AIMS: We investigated whether plasma lactate dehydrogenase (LDH) predicts outcome in hypothermia (HT)-treated term infants with moderate/severe hypoxic-ischaemic encephalopathy (HIE) and additionally whether LDH differs between infants with evidence for acute and nonacute perinatal insults and postnatal collapse (PNC). METHODS: Data from HT-treated infants with HIE (n = 39) were analysed retrospectively. Adverse outcome was defined as a Mental and/or Psychomotor Developmental Index (Bayley Scales of Infant Development II), at 18 months <70. The likely timing of insult onset was assessed in infants with an LDH sample obtained within 6 h of birth or PNC (n = 20). RESULTS: LDH differed between the favourable/adverse outcome groups at the end of HT treatment (median (IQR) 1540 (1400-1950)U/L vs. 3555 (3003-8705)U/L, (p < 0.01)). All infants (n = 22) with LDH <2085U/L had a favourable outcome while 6 of 11 infants with LDH ≥ 2085U/L had an adverse outcome. LDH in those who died (n = 4) was higher than the favourable outcome group (5090 (2915-12222)U/L, (p < 0.01)) but sampled earlier. Early LDH differed significantly (p < 0.01) between infants with evidence for acute or nonacute insults or PNC. CONCLUSION: THESE results offer a biomarker, with high negative predictive value in the assessment of outcome in HT-treated term infants, needing prospective validation.