Preterm white matter injury: ultrasound diagnosis and classification.

White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective studies.

The impact of intrauterine and extrauterine weight gain in premature infants on later body composition.

BackgroundThe impact of intrauterine and extrauterine growth on later insulin resistance and fat mass (FM) in very low birth weight (VLBW) infants is not well established. The aim of our study was to evaluate the effects of intrauterine and early/late extrauterine growth on later insulin resistance and body composition in VLBW infants from 6 months' corrected age (CA) to 36 months.MethodsProspective measurements of body composition by dual-energy X-ray absorptiometry and insulin resistance by homeostasis model assessment insulin resistance (HOMA-IR) along with other fasting plasma biochemistries were made in 95 VLBW infants at 6, 12, 18, and 24 months' CA and 36 months' postnatal age. Mixed-effect models were used to evaluate the effects of age, sex, maturation status, and Δweight SD score on percentage FM (PFM), FM index (FMI), fat-free mass index (FFMI), and HOMA-IR.ResultsPFM and FMI were negatively associated with a decrease in weight-SD scores from birth to 36 weeks' postmenstrual age (PMA; P=0.001) and from 36 weeks' PMA to 6 months' CA (P=0.003). PFM and FMI were higher in AGA than in small for gestational age (SGA) infants. HOMA-IR was not associated with the Δweight-SD scores in either period.ConclusionsCatch-down growth in terms of weight is associated with persistently lower adiposity but not insulin resistance up to 36 months of age.

Risk Factors for Neonatal Arterial Ischemic Stroke: The Importance of the Intrapartum Period.

OBJECTIVE: To investigate risk factors for neonatal arterial ischemic stroke (NAIS), and compare them with those present in term controls and infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Antepartum and intrapartum data were collected at presentation from 79 infants with NAIS and compared with 239 controls and 405 infants with HIE. The relationships between risk factors and NAIS were explored using univariable and multivariable regression. RESULTS: Compared with controls, infants with NAIS more frequently had a family history of seizures/neurologic diseases, primiparous mothers, and male sex. Mothers of infants with NAIS experienced more intrapartum complications: prolonged rupture of membranes (21% vs 2%), fever (14% vs 3%), thick meconium (25% vs 7%), prolonged second stage (31% vs 13%), tight nuchal cord (15% vs 6%), and abnorm8al cardiotocography (67% vs 21%). Male sex (OR 2.8), family history of seizures (OR 6.5) or neurologic diseases (OR 4.9), and ≥1 (OR 5.8) and ≥2 (OR 21.8) intrapartum complications were independently associated with NAIS. Infants with NAIS and HIE experienced similar rates though different patterns of intrapartum complications. Maternal fever, prolonged rupture of membranes, prolonged second stage, tight nuchal cord, and failed ventouse delivery were more common in NAIS; thick meconium, sentinel events, and shoulder dystocia were more frequent in HIE. Abnormal cardiotocography occurred in 67% of NAIS and 77.5% of infants with HIE. One infant with NAIS and no infant with HIE was delivered by elective cesarean (10% of controls). CONCLUSIONS: NAIS is multifactorial in origin and shares risk factors in common with HIE. Intrapartum events may play a more significant role in the pathogenesis of NAIS than previously recognized.

Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy had favourable outcomes at a referral hospital in a middle-income country.

AIM: This South African study documented the survival and neurodevelopmental outcomes of infants with hypoxic-ischaemic encephalopathy (HIE) after introducing cooling to a neonatal intensive care unit and identified early markers for neurodevelopmental outcome. METHODS: We retrospectively reviewed infants that received cooling according to the Total Body Hypothermia trial protocol from 2008 to 2011. Infants were screened with the Bayley Scales of Infant and Toddler Development, Third Edition, at one year of age and underwent neurological and hearing assessments. RESULTS: Data on 99 infants with HIE showed that 45% of cases were moderate, 23% severe and 32% mild. An abnormal amplitude integrated electro-encephalogram (aEEG) background was documented in 45 cases within 24 hours. Magnetic resonance imaging (MRI) scans were consistent with HIE in all but one case. We reviewed 50 traceable survivors at one year. Development was significantly impaired in nine and 41 were normal or mildly impaired. A severely abnormal aEEG background, severe HIE and an abnormal MRI were associated with death and severe impairment. A good suck, mild HIE, primiparity and normal MRI were associated with good outcomes. CONCLUSION: Most infants with HIE survived without major impairment. Previously described predictors of neurodevelopmental outcome were good surrogate markers in this population.

Preterm cranial ultrasound scanning is both feasible and effective in a middle-income country.

AIM: Cranial ultrasound is seldom used in middle-income countries, and the burden of preterm brain injury and its relationship to perinatal data is unknown. We assessed cranial ultrasound abnormalities in very low-birthweight (VLBW) infants and correlated the findings with perinatal data. METHODS: VLBW Armenian infants receiving neonatal intensive care in 2012 were scanned from birth to term-equivalent age (TEA). Clinical data were collected prospectively. RESULTS: We studied 100 VLBW infants with a median gestation of 30 weeks. Periventricular white matter echogenicity (PVE) lasting more than two weeks was seen in 34 infants, grade III intraventricular haemorrhage (IVH) in 10, haemorrhagic parenchymal infarction (HPI) in seven and cystic periventricular leukomalacia in two. Caudothalamic notch echogenicity appeared in 36 infants after two to three weeks, with cystic transformation in 22. At TEA, 17 infants had persisting PVEs and 55 had increased basal ganglia/thalamic (BGT) echogenicity. Lack of antenatal steroids was significantly associated with IVH and HPI and intubation at birth with IVH. Late BGT echogenicity was generally seen in infants without perinatal problems. CONCLUSION: Our study demonstrated that cranial ultrasound can be used effectively in a middle-income country to identify high-risk infants and monitor quality of care.

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.

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.

Behavioral Problems and Family Impact in Congenital Cytomegalovirus Infection.

We examined behavior (Child Behavior Checklist) and family functioning (Family Impact Questionnaire) in 65 children with congenital cytomegalovirus. Behavioral problems were present in 30.8%. Parents of children with moderate/severe outcomes reported strain on all areas of family functioning. Behavioral problems were associated with negative impact on parental feelings and marital/partnership relationship. Our findings inform planning support services.

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.

Clinical, biochemical, and neuroimaging findings predict long-term neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To evaluate clinical, biochemical, and neuroimaging findings as predictors of neurodevelopmental outcome in patients with symptomatic congenital cytomegalovirus (CMV). STUDY DESIGN: The study cohort comprised 26 patients with symptomatic congenital CMV born between 1993 and 2009 in a single center. Absolute and weight deficit-adjusted head circumference were considered. Cerebrospinal fluid (CSF) investigations included standard cytochemical analysis, determination of beta2-microglobulin (ß2-m), neuron-specific enolase, and CMV DNA detection. Neuroimaging was classified according to a validated scoring system comprising calcifications, ventriculomegaly, and atrophy, with findings graded from 0 to 3. Systematic long-term neurodevelopmental assessment included motor function, cognition, behavior, hearing, vision, and epilepsy. Sequelae were graded as mild/absent, moderate, or severe; adverse outcome was defined as death or moderate to severe disability. RESULTS: Three children died. The mean age at follow-up of the survivors was 8.7 ± 5.3 years (range, 19 months to 18.0 years). Neonatal findings showing a significant association with adverse outcome were relative microcephaly, CSF ß2-m concentrations, and grade 2-3 neuroimaging abnormalities (P < .05). Receiver operator characteristic curve analysis indicated that the most accurate single factor for predicting unfavorable outcome was CSF ß2-m >7.9 mg/L (area under the curve, 0.84 ± 0.08; sensitivity, 69%; specificity, 100%). The combination of CSF ß2-m >7.9 mg/L and moderate-severe neuroimaging alterations improved predictive ability (area under the curve, 0.92 ± 0.06; sensitivity, 87%; specificity, 100%). CONCLUSION: Adjusted head circumference, CSF ß2-m level, and neuroimaging studies have prognostic significance for neurodevelopmental outcome in newborns with congenital CMV. A combination of early findings improves the predictive value.

White matter and cortical injury in hypoxic-ischemic encephalopathy: antecedent factors and 2-year outcome.

OBJECTIVE: To examine the spectrum of isolated white matter (WM)/cortical injury and its relation to outcomes in infants with hypoxic-ischemic encephalopathy (HIE) and normal appearing basal ganglia and thalami. STUDY DESIGN: From 1992-2007, 84 term infants with HIE and normal basal ganglia and thalami on neonatal magnetic resonance imaging were studied; WM/cortical lesions were classified by site and severity. Neurodevelopmental outcomes and head growth were documented at a median age of 2 years. RESULTS: The WM was normal or mildly abnormal in 33.5%, moderate in 40.5%, and severely abnormal in 26% of infants. Cortical involvement was not seen or was only mild in 75.5%, moderate in 13%, and severe in 12% of infants. WM and cortical injury severity were highly correlated (Spearman ρ = 0.74; P < .001). Infants with severe WM injury had more severe neonatal courses and a higher incidence of hypoglycemia. No infant died. Five infants (6%) developed cerebral palsy but all could walk independently. Cognitive, visual, language, behavioral, and seizure problems were highly prevalent and correlated significantly with the severity of WM injury and poor postnatal head growth. CONCLUSION: Infants with HIE and selective WM/cortical injury have a low prevalence of cerebral palsy but have a wide range of other problems, which occur more often with severe WM/cortical lesions.

Perinatal morbidity and risk of hypoxic-ischemic encephalopathy associated with intrapartum sentinel events.

OBJECTIVE: To examine perinatal morbidity and rate of hypoxic-ischemic encephalopathy in infants exposed to intrapartum sentinel events. STUDY DESIGN: Retrospective cohort study from 2000-2005. Perinatal mortality, perinatal morbidity and rate of hypoxic-ischemic encephalopathy were compared in 3 groups of infants exposed to different risk factors for perinatal asphyxia (sentinel events, nonreassuring fetal status, elective cesarean section). RESULTS: Five hundred eighty-six infants were studied. Perinatal mortality was 6% in the sentinel event group and 0.3% in the nonreassuring fetal status group (relative risk, 2.4; 95% confidence interval, 1.95-2.94). Perinatal morbidity was 2-6 times more frequent in infants exposed to sentinel events; the incidence of hypoxic-ischemic encephalopathy was 10%, compared with 2.5% in the nonreassuring fetal status group (relative risk, 1.93; 95% confidence interval, 1.49-2.52). No infant in the elective cesarean section group died, had perinatal morbidity, or developed encephalopathy. CONCLUSION: Intrapartum sentinel events are associated with a high incidence of perinatal morbidity and hypoxic-ischemic encephalopathy.

Prediction of outcome from MRI and general movements assessment after hypoxic-ischaemic encephalopathy in low-income and middle-income countries: data from a randomised controlled trial.

OBJECTIVE: To evaluate the accuracy of neonatal MRI and general movements assessment (GMA) in predicting neurodevelopmental outcomes in infants with hypoxic-ischaemic encephalopathy (HIE). DESIGN: Secondary analyses of a randomised controlled trial (RCT). SETTING: Tertiary neonatal intensive care unit in India. METHODS: Fifty infants with HIE were included in an RCT of therapeutic hypothermia (25 cooled and 25 non-cooled). All infants underwent brain MRI at day 5, GMA at 10-15 weeks and outcome assessments including Bayley Scales of Infant and Toddler Development, third edition, at 18 months. Associations between patterns of brain injury, presence/absence of fidgety movements (FMs) and outcomes were assessed. RESULTS: Seventeen of 47 (36%) had adverse outcome (5 (21%) cooled vs 12 (52%) non-cooled, p=0.025). Eight infants died (four before an MRI, another three before GMA). Two developed severe cerebral palsy and seven had Bayley-III motor/cognitive composite score <85. Twelve (26%) had moderately/severely abnormal MRI and nine (23%) had absent FMs. The positive predictive value (95% CI) of an adverse outcome was 89% (53% to 98%) for moderate/severe basal ganglia and thalami (BGT) injury, 83% (56% to 95%) for absent/equivocal signal in the posterior limb of the internal capsule (PLIC) and 67% (38% to 87%) for absent FMs. Negative predictive values (95% CI) were 85% (74% to 92%) for normal/mild BGT injury, 90% (78% to 96%) for normal PLIC and 86% (74% to 93%) for present FMs. CONCLUSIONS: Neonatal MRI and GMA predicted outcomes with high accuracy in infants with HIE. The GMA is a feasible low-cost method which can be used alone or complementary to MRI in low-resource settings to prognosticate and direct follow-up. TRIAL REGISTRATION NUMBER: CTRI/2013/05/003693.

General movements in full-term infants with perinatal asphyxia are related to Basal Ganglia and thalamic lesions.

OBJECTIVE: To correlate the site and severity of brain lesions seen on magnetic resonance imaging (MRI) with the quality of general movements in term infants with hypoxic-ischemic encephalopathy (HIE) and compare the prognostic value of general movements and MRI for motor outcome. STUDY DESIGN: Early brain MRI scans in 34 term infants with HIE not treated with hypothermia were reviewed and scored for site of injury and lesion pattern by an experienced neuroradiologist. General movement quality and trajectories at 1 and 3 postnatal months were evaluated. Motor outcome was assessed at 24 months. RESULTS: MRI scores for the basal ganglia and thalami, posterior limb of the internal capsule, white matter, and cortex and lesion patterns were correlated with 1-month and 3-month general movements and general movement trajectories; central gray matter scores were correlated most strongly with cramped-synchronized general movements and abnormal motor outcome. MRI scores were 100% sensitive and 72.2% specific for motor outcome, and cramped-synchronized general movements were 100% specific and 68.7% sensitive for motor outcome. CONCLUSIONS: In term infants with HIE, the site and severity of brain lesions seen on early MRI are highly correlated with general movements. Central gray matter damage leads to cramped-synchronized general movements and poor motor outcome. Early MRI scans and general movements are complementary tools for predicting motor outcome.

MRI combined with early clinical variables are excellent outcome predictors for newborn infants undergoing therapeutic hypothermia after perinatal asphyxia.

BACKGROUND: Binary prediction-models for outcome [death, cognition, presence and severity of cerebral palsy (CP)], using MRI and early clinical data applicable for individual outcome prediction have not been developed. METHODS: From Dec 1st 2006 until Dec 31st 2013, we recruited 178 infants into a population-based cohort with moderate or severe hypoxic-ischaemic encephalopathy (HIE) including postnatal collapse (PNC, n = 12) and additional diagnoses (n = 12) using CoolCap/TOBY-trial entry-criteria including depressed amplitude-integrated EEG (aEEG). Early clinical/biochemical variables and MRI scans (median day 8) were obtained in 168 infants. Injury severity was scored for cortex, basal ganglia/thalami (BGT), white matter (WM) and posterior limb of the internal capsule, summating to a total injury score (TIS, range 0-11). Outcome was categorized as adverse or favourable at 18-24 months from Bayley-III domains (cut-off 85) and neurological examination including CP classification. FINDINGS: HIE and entry-aEEG severity were stable throughout the study. Outcome was favourable in 133/178 infants and adverse in 45/178: 17 died, 28 had low Cognition/Language scores, (including 9 with severe CP and 6 mild); seven had mild CP with favourable cognitive outcome. WMxBGT product scores and TIS were strong outcome predictors, and prediction improved when clinical/biochemical variables were added in binary logistic regression. The Positive Predictive Value for adverse outcome was 88%, increasing to 95% after excluding infants with PNC and additional diagnoses. Using WMxBGT in the regression predicted 8 of the 9 children with severe CP. INTERPRETATION: Binary logistic regression with WMxBGT or TIS and clinical variables gave excellent outcome prediction being 12% better than single variable cross-tabulation. Our MRI scoring and regression models are readily accessible and deserve investigation in other cohorts for group and individual prediction. FUNDING: We thank the National Health Service (NHS) and our Universities and funders in UK and Norway: SPARKS, The Moulton Foundation, The Norwegian Research Council, The Lærdal Foundation for Acute Medicine and charitable donations for their support for cooling therapy.

Usefulness of video recordings for validating neonatal encephalopathy exams: a population-based cohort study.

OBJECTIVE: To determine the usefulness of video recordings for validating neonatal encephalopathy (NE) exams. DESIGN: Population-based prospective cohort study. NE was assessed and recorded at 1, 3 and 5 hours after birth by the attending physician. Recordings were reviewed blindly after the recruitment period by two specialists. Outcome was assessed at 36 months of age. SETTING: Twelve intensive care units in Spain. PATIENTS: Infants of ≥35 weeks' gestational age with perinatal asphyxia. MAIN OUTCOMES MEASURES: Weighted kappa to measure disagreement between the two specialists and between the attending physician and the specialists' classification agreed on by consensus. Regression models to test the association of disagreement on NE assessment and outcome. RESULTS: Of the 32 325 liveborn infants, 217 met the inclusion criteria. Video-recordings were not available for 43 infants (20%). Weighted kappa statistic was 0.74 (95% CI 0.67 to 0.81) between the specialists and the attending physicians. Disagreement occurred in 93 of the 417 (22%) videos, specifically in 39 (14%), 43 (47%), 11 (34%) and 0 exams categorised as no, mild, moderate and severe NE, respectively. According to the specialist consensus assessment, there was disagreement on the therapeutic hypothermia decision in 10 infants.When there was consensus among the specialists assessing a more severe NE degree compared with the attending physicians in 170 infants, those infants had lower cognitive scores with a median of -5.33 points (95% CI -9.85 to -8.16; p=0.02). CONCLUSIONS: This study supports the feasibility and benefit of using video recordings to identify NE in infants with perinatal asphyxia.

Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy in India (THIN study): a randomised controlled trial.

OBJECTIVE: To evaluate the neuroprotective effect of therapeutic hypothermia (TH) induced by phase changing material (PCM) on MRI biomarkers in infants with hypoxic-ischaemic encephalopathy (HIE) in a low-resource setting. DESIGN: Open-label randomised controlled trial. SETTING: One neonatal intensive care unit in a tertiary care centre in India. PATIENTS: 50 term/near-term infants admitted within 5 hours after birth with predefined physiological criteria and signs of moderate/severe HIE. INTERVENTIONS: Standard care (n=25) or standard care plus 72 hours of hypothermia (33.5°C±0.5°C, n=25) induced by PCM. MAIN OUTCOME MEASURES: Primary outcome was fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC) on neonatal diffusion tensor imaging analysed according to intention to treat. RESULTS: Primary outcome was available for 22 infants (44%, 11 in each group). Diffusion tensor imaging showed significantly higher FA in the cooled than the non-cooled infants in left PLIC and several white matter tracts. After adjusting for sex, birth weight and gestational age, the mean difference in PLIC FA between groups was 0.026 (95% CI 0.004 to 0.048, p=0.023). Conventional MRI was available for 46 infants and demonstrated significantly less moderate/severe abnormalities in the cooled (n=2, 9%) than in the non-cooled (n=10, 43%) infants. There was no difference in adverse events between groups. CONCLUSIONS: This study confirmed that TH induced by PCM reduced brain injury detected on MRI in infants with moderate HIE in a neonatal intensive care unit in India. Future research should focus on optimal supportive treatment during hypothermia rather than looking at efficacy of TH in low-resource settings. TRIAL REGISTRATION NUMBER: CTRI/2013/05/003693.

Perinatal arterial ischemic stroke.

Perinatal arterial ischemic stroke is a relatively common and serious neurologic disorder that can affect the fetus, the preterm, and the term-born infant. It carries significant long-term disabilities. Herein we describe the current understanding of its etiology, pathophysiology and classification, different presentations, and optimal early management. We discuss the role of different brain imaging modalities in defining the extent of lesions and the impact this has on the prediction of outcomes. In recent years there has been progress in treatments, making early diagnosis and the understanding of likely morbidities imperative. An overview is given of the range of possible outcomes and optimal approaches to follow-up and support for the child and their family in the light of present knowledge.