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Aim Methods Results Conclusion A study reported that therapeutic hypothermia (TH) did not reduce the combined prognosis of mortality and disability at 18 months, in low‐ and middle‐income countries for patients with hypoxic ischaemic encephalopathy (HIE) who received TH, suggesting its no implementation in these regions.We described characteristics, mortality, and neurological response before and after the use of TH in newborns with HIE within the EpicLatino Neonatal Network (ENN) and described the population of infants with HIE treated and not treated with TH.Data were collected from 2015 to 2022 for patients with HIE. Mortality rates and Sarnat scores were compared before and after TH. The Wilcoxon Signed‐Rank Test was used for comparisons.In this observational study 518 neonates of our total population of 26 970, had HIE (1.92%) of whom 150 underwent TH. Ten out of 21 neonatal intensive care units (NICUs) provided TH. The Wilcoxon Signed Rank Test for 138 cases with complete data showed a significant difference.The findings support the benefits of TH in HIE within this cohort. TH should not be withheld solely due to the economic status of the country. A strict patient selection and TH protocol are essential. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Immune dysregulation and delayed onset of sleep wake cycling (SWC) are associated with worse outcome in neonatal encephalopathy (NE), however the association between sleep and immune dysfunction in NE remains unclear. Aimed to evaluate association of sleep and systemic inflammation with outcomes in NE.Amplitude‐integrated electroencephalography (aEEG) recordings were collected on infants undergoing therapeutic hypothermia (TH). Duration to onset of (SWC) and sleep quality (SQ) were examined. Blood samples collected during the first 2 days of life. Thirteen pro‐ and anti‐inflammatory serum cytokines were quantified. Adverse outcome defined as death or abnormal MRI brain.Earlier onset of SWC and better SQ had less adverse outcomes. SQ provided better prognostic value and showed better interobserver agreement compared to duration to SWC. Better SQ associated with lower cytokines EPO and interleukin (IL)‐1β. In infants with unfavourable outcome, shorter duration to SWC was associated with higher EPO and better SQ was associated with lower TNF‐α.Earlier onset of SWC or better SQ showed less systemic inflammation and fewer adverse outcomes. SQ during TH provided better prognostic information than time of onset of SWC. Modulation of circadian rhythm in infants with NE may have an immunomodulatory role, leading to improved outcomes. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion CoolCuddle, enabling parents to cuddle their babies with neonatal encephalopathy (NE) during therapeutic hypothermia and intensive care (TH), was developed in research settings. To determine the impact of implementing CoolCuddle in usual care in six diverse neonatal intensive care units on the cooling process and intensive care.This vital sign cohort study embedded within the CoolCuddle implementation study enrolled 36 infants receiving TH for NE. Nurses received training on CoolCuddle and a standard operating procedure using an instruction video. After consenting, parents experienced up to 2 h of CoolCuddle with 30 min of pre‐ and post‐cuddle observation. We used multilevel, clustered linear modelling to assess the physiological stability in temperature, cardio‐respiratory and neurophysiology across the CoolCuddle.In 60 CoolCuddles over 93.12 h, respiratory parameters, heart rate or neurological function did not vary between the epochs (p > 0.05). During cuddle, sleep–wake cycling on amplitude‐integrated EEG increased (p = 0.008) and there was weak evidence of lower pain scores (p = 0.08). No adverse effects were observed.Implementing CoolCuddle with support in usual practice maintained physiological stability and did not significantly affect the cooling process or intensive care, and may improve infant comfort. Ongoing monitoring of adverse effects when implementing CoolCuddle is recommended. [ABSTRACT FROM AUTHOR]

Aim: To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. Methods: In this prospective study, we enrolled 25 uninfected full‐term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. Results: In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut‐off but not those of presepsin. Conclusion: In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to determine whether overcooling (temperature <33°C) during passive hypothermia when transporting neonates with perinatal asphyxia increased the risk of short‐term neurological injury. Methods: A retrospective observational study was performed. Newborns transferred to the LaCardio neonatal unit between January 2021 and April 2022 with moderate and severe perinatal asphyxia and who received passive hypothermia during transport were included. A temperature of <33°C was considered overcooling. A composite outcome of neurological injury was defined by the presence of abnormalities on brain magnetic resonance imaging, video telemetry, seizure before discharge or both. Results: The study included 101 newborns. A total of 18 neonates had a temperature <33°C after transportation. Neurological injuries were present in 21.8% of the temperature <33°C group and 78.2% of the temperature ≥33°C group. Temperature <33°C at the end of transport (aOR 9.2, 95% CI 1.1–77.3) were associated with neurological injury before discharge from the unit. Conclusion: During transportation, overcooling in neonates with asphyxia increases the risk of neurological injury before discharge from the neonatal unit. It is important to qualify the transport team with adequate training and equipment for therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support for 18‐month composite outcomes in infants with hypoxic‐ischaemic encephalopathy treated with hypothermia. Methods: This retrospective, nationwide, observational study focused on newborn infants registered in Japan's Baby Cooling Registry between 1 January 2012 and 31 December 2016. The adverse outcomes were defined as death or survival with cerebral palsy, visual or auditory impairment or the requirement for mechanical ventilation or tube feeding at 18 months of age. Results: Adverse outcomes occurred in 165 (28%) of the 591 children in the final cohort. These were predicted by prolonged dependence on mechanical ventilation or tube feeding for more than seven and more than 14 days. The respective values were positive predictive value 0.34 (95% CI 0.33–0.34) and 0.60 (95% CI 0.56–0.62), negative predictive value 0.97 (95% CI 0.91–0.99) and 0.93 (95% CI 0.90–0.95) and area under the curve 0.59 (95% CI 0.54–0.64) and 0.81 (95% CI 0.77–0.85). Conclusion: Prolonged dependence on mechanical ventilation or tube feeding for more than 14 days may be useful in predicting 18‐month outcomes in newborn infants who have received therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Aim: Hypocarbia in the early postnatal period might exacerbate brain injury in babies with hypoxic ischaemic encephalopathy following birth asphyxia. This mini‐review summarised studies on pCO2 values that were monitored periodically in term newborns with moderate/severe hypoxic–ischaemic encephalopathy and correlated with short or long‐term outcomes. Methods: We searched the databases MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), web of science and the Cochrane Library and identified nine studies. Results: Among the nine included studies, therapeutic hypothermia was administered in seven studies. In most studies, blood pCO2 levels were measured from birth till 72 h of life or till the endpoint of therapeutic hypothermia. Eight studies showed that any hypocarbia (moderate or severe, or cumulative) was associated with an increased risk of adverse outcomes in the form of brain injury in MRI, death or neurodevelopmental disability. Conclusion: Hypocarbia could lead to adverse short‐term and long‐term outcomes despite therapeutic hypothermia in neonates with HIE. Hence, it is vital to monitor pCO2 levels closely in these infants and consider strategies to maintain pCO2 levels in the normal range. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate how individual markers for birth asphyxia, so‐called A criteria, were associated with the probability of receiving therapeutic hypothermia. Methods: This population‐based cohort study included 1336 live‐born singleton term infants with any A criterion in the Stockholm‐Gotland Region, Sweden during 2008 to 2014. The Swedish Neonatal Quality Register and National Patient Register were used for data collection. Results were presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results: There were 89 infants, 44 boys and 45 girls with mean gestational age 40.5 weeks, who received therapeutic hypothermia. Low Apgar score, aOR 12.44 (95% CI 5.99–25.86), and resuscitation, aOR 9.18 (95% CI 3.77–22.34), were strongly associated with therapeutic hypothermia. A pH <7.0 was less associated with the outcome, aOR 2.02 (95% CI 1.02–4.0). No infant who received therapeutic hypothermia fulfilled the criteria of base deficit ≥16 mmol/L only. Conclusion: A low Apgar score of and/or a need for resuscitation is more relevant for identifying infants eligible for therapeutic hypothermia, compared to other A criteria. This knowledge could be used clinically to identify cases for review and avoid unnecessary monitoring of infants. [ABSTRACT FROM AUTHOR]

Aim: We reviewed the literature on cooling methods during transport of newborn infants with hypoxic‐ischaemic encephalopathy (HIE) born in a non‐tertiary centre and transferred to a neonatal intensive care unit for therapeutic hypothermia. Methods: The electronic databases CENTRAL, MEDLINE, Embase, CINAHL, and Scopus were searched from inception up to 8 March 2022 for studies comparing cooling versus no cooling, active versus passive cooling, and servo‐controlled versus non‐servo‐controlled cooling. Odds ratio and confidence of interval were calculated for dichotomous outcomes and mean difference and confidence interval for continuous outcomes. Results: The final analysis included 14 studies, 1 randomised and 13 non‐randomised, involving 1098 newborn infants. Compared with the other cooling methods, servo‐controlled active cooling was more likely to maintain body temperature within the target range of 33°C–34°C on arrival at a neonatal intensive care unit: odds ratio 13.58, 95% confidence interval 4.32–42.66, risk difference 0.33, 95% confidence interval 0.19–0.46; 224 participants; three studies; I2 0%. The certainty of evidence was low. Only five studies reported mortality rates. Conclusion: Servo‐controlled active cooling may be the preferred method during transport of newborn infants with HIE. A future area of focus should be long‐term neurodevelopmental outcomes after servo‐controlled active cooling. [ABSTRACT FROM AUTHOR]

Aim: We aimed to determine whether children with neonatal Hypoxic Ischaemic Encephalopathy (HIE) treated with therapeutic hypothermia (TH) differ from their peers on measures of fine motor skills, executive function, language and general cognitive abilities, factors that are important for school readiness. Methods: We compared school readiness in 31children with HIE treated with TH (without Cerebral Palsy; mean age 5 years 4 months) with 20 typically developing children without HIE (mean age 5 years 6 months). Results: Children with HIE scored significantly lower than typically developing children on fine motor skills, executive functions, memory and language. Conclusion: While general cognitive abilities and attainment were in the normal range, our findings suggest those scores mask specific underlying difficulties identified by more focussed assessments. Children with HIE treated with TH may not be as 'school ready' as their typically developing classmates and may benefit from long‐term follow‐up until starting school. [ABSTRACT FROM AUTHOR]

Aim: Since therapeutic hypothermia (TH) is known for its inhibitory effects on leucocyte migration and cytokine synthesis, our aim was to underline the necessity of early monitoring for potential immunomodulatory risks. Methods: Using a 13‐year retrospective case‐control study at the paediatric intensive care unit (PICU) of the Medical University in Vienna, all newborn infants and children receiving TH were screened and compared with a diagnosis‐matched control group undergoing conventional normothermic treatment (NT). TH was accomplished by using a non‐invasive cooling device. Target temperature was 32‐34°C. Children with evident infections, a medical history of an immunodeficiency or undergoing immunosuppressive therapy, were excluded. Results: During the observational period, 108 patients were screened, 27 of which underwent TH. Culture‐proven infections occurred in 22% of the TH group compared with 4% of the normothermic controls (P =.1). From the second day following PICU admission, median C‐reactive protein (CRP) values were higher in the TH group (day two P =.002, day three P =.0002, day six P =.008). Conclusion: Children undergoing TH showed earlier and higher increases in CRP levels when compared to normothermic controls. These data underline the necessity of early and continuous monitoring for possible infectious complications. [ABSTRACT FROM AUTHOR]

Aim: The knowledge is limited about how parents experience the time when their infant is receiving therapeutic hypothermia (TH) after severe perinatal asphyxia. The aim of this study was to explore parents' experience of closeness and involvement in their infant's care while in the neonatal intensive care unit (NICU) with their newborn undergoing TH. Methods: Face‐to‐face, semi‐structured interviews were conducted with parents (n = 11) whose infants (n = 8, aged 3‐5 years at the time of the study) underwent TH at a level III Swedish NICU during 2013‐2016. The interviews were analysed using qualitative content analysis. Results: All the parents shared the trauma of being both physically and psychologically separated from their infant. They all described a need for information and emotional support, and reported that the NICU staff had influenced the extent to which they as parents had been able to be near and actively participate in the care. Parents described the wish to be closer to their infant and to be more actively involved in their infant's care. Conclusion: Strategies to enable parent‐infant closeness and active guidance from staff might help alleviate the emotional stress of parents and promote their participation during TH. [ABSTRACT FROM AUTHOR]

Aim: To evaluate whether phase-changing material can be used for therapeutic hypothermia of asphyxiated newborns in low-resource settings.Methods: Prospective interventional study of asphyxiated term infants fulfilling criteria for hypothermia treatment at Vietnam National Children's Hospital from September 2014 to September 2016. Hypothermia was induced within 6 hours after birth and maintained for 72 hours by a phase-changing material mattress with melting point of 32°C. Rectal temperature was continuously measured, and deviations from target temperature range 33.5-34.5°C were recorded.Results: In total 52 infants (mean gestational age 39.3 ± 1.1 weeks) included and cooled, the median temperature at initiation of cooling was 35.3 (IQR 34.5-35.9)°C. The median time to reach target temperature was 2.5 (IQR 2-3) hours. The mean temperature during the cooling phase was 33.95 ± 0.2°C. Throughout the cooling phase, the target temperature range (33.5-34.5°C) was maintained more than 80% of the time. Rate of rewarming was 0.5 ± 0.14°C/hour.Conclusion: Phase-changing material can be used as an effective cooling method. Though not a servo-controlled system, it is easy to induce hypothermia, maintain target temperature and rewarm infants in a slow and controlled manner without need for frequent changes and minimum risk of skin injury. [ABSTRACT FROM AUTHOR]

Aim: Troponin is a sensitive marker of asphyxia in term infants mirroring the myocardial injury sustained in global hypoxia-ischaemia. In addition, troponin is a sensitive marker of severity of stroke in adults and neonatal encephalopathy (NE). We aimed to examine the relationship between troponin T in infants with perinatal asphyxia and brain injury on MRI and correlate with neurodevelopmental outcome.Methods: Serum troponin was sampled in infants requiring resuscitation at birth and/or neonatal encephalopathy in a tertiary referral neonatal centre. Birth history, clinical parameters, neuroimaging and developmental outcome (Bayley Scores of Infant Development [BSID] III) were evaluated.Results: Infants with perinatal asphyxia (n = 54) had serum troponin T measured and 27 required therapeutic hypothermia. Troponin T levels on days 1 and 2 were predictive of need for TH, development of seizures and grade II/III NE (AUC = 0.7; P-values < .001), troponin T levels on days 1, 2 and 3 were highly significant predictors of mortality (AUC = 0.99, P-values .005). The cut-off values of troponin T for best prediction of mortality were 0.84, 0.63 and 0.58 ng/mL on days 1, 2 and 3, respectively. Troponin T on day 3 of life was predictive of injury in the combined area of basal ganglia/watershed on MRI (AUC 0.70; P-value = .045).Conclusion: Infants with brain injury on neuroimaging following perinatal asphyxia had significantly elevated serum troponin, and troponin also correlated with developmental scores at 2 years. Further studies combining troponin and MRI may assist in the classification of neonatal brain injury to define aetiology, prognosis and response to treatment. [ABSTRACT FROM AUTHOR]

Aim: To investigate the characteristics of infants with neonatal encephalopathy (NE) receiving therapeutic hypothermia (TH) who developed late onset oxygen requirement during or after rewarming.Methods: Infants were stratified by receiving (a) new onset isolated oxygen requirements during or after rewarming; (b) no respiratory support during hospital stay; and (c) invasive and/or non-invasive respiratory support before or during cooling.Results: Of 136 infants treated with TH, 49 (36%) did not require any respiratory support, and 78 (57.4%) received invasive or non-invasive support before or during cooling. Nine infants (6.6%) developed late onset oxygen requirement. The late onset oxygen requirement started at median age of 3.8 days (IQR 3.6-5.2) and ended at median 7.5 days (IQR 5.8-12.7). Total hours of O2 exposure were median 62.0 (IQR 24.4-112.6). Maximum support was low-flow nasal cannula from 100% oxygen source with a flow rate of 40-250 mL/min. Infants in this group had higher Apgar scores, milder metabolic acidosis and no seizures. Three infants had diagnostic investigations without significant findings.Conclusion: A small percentage of neonates with NE developed late onset oxygen requirement during or after rewarming. Late oxygen requirement was associated with evidence of less severe perinatal hypoxia-ischaemia. [ABSTRACT FROM AUTHOR]

Aim: The role of machine learning on clinical documentation for predictive outcomes remains undefined. We aimed to compare three neural networks on inpatient providers' notes to predict mortality in neonatal hypoxic-ischaemic encephalopathy (HIE).Methods: Using Children's Hospitals Neonatal Database, non-anomalous neonates with HIE treated with therapeutic hypothermia were identified at a single-centre. Data were linked with the initial seven days of documentation. Exposures were derived using the databases and applying convolutional and two recurrent neural networks. The primary outcome was mortality. The predictive accuracy and performance measures for models were determined.Results: The cohort included 52 eligible infants. Most infants survived (n = 36, 69%) and 23 had severe HIE (44%). Neural networks performed above baseline and differed in their median accuracy for predicting mortality (P = .0001): recurrent models with long short-term memory 69% (25th , 75th percentile 65, 73%) and gated-recurrent model units 65% (62, 69%) and convolutional 72% (64, 96%). Convolutional networks' median specificity was 81% (72, 97%).Conclusion: The neural network models demonstrated fundamental validity in predicting mortality using inpatient provider documentation. Convolutional models had high specificity for (excluding) mortality in neonatal HIE. These findings provide a platform for future model training and ultimately tool development to assist clinicians in patient assessments and risk stratifications. [ABSTRACT FROM AUTHOR]

Aim: The adequate dosing of topiramate in neonates undergoing therapeutic hypothermia has not been established. The aim of this study was to design a dosing schedule capable of providing topiramate serum concentrations within the accepted therapeutic range.Methods: Neonates (n = 52) with hypoxic ischaemic encephalopathy and subjected to therapeutic hypothermia were dosed with topiramate, 5 mg/kg on day one and 3 mg/kg on days two to five, to decrease seizure events. A total of 451 topiramate serum concentrations obtained in the patients were used to develop a population pharmacokinetic model using a non-linear mixed-effects modelling approach.Results: A one-compartment model with first-order absorption and two different clearance terms, one for the cooling period and another for the post-warming period, were used to describe the concentration-time topiramate data. The probability of no-seizure events could not be related to topiramate concentrations, which was attributed to excessively low topiramate concentrations. A modified dosage schedule was designed with the aim of obtaining more than 90% of patients with topiramate concentrations within the therapeutic range after the first dose.Conclusion: The dosage schedule of topiramate in these patients should be modified with the aim of decreasing the frequency of seizure events. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether motor performance in school-age children without cerebral palsy (CP), cooled for neonatal encephalopathy, is associated with perinatal factors and 18-month developmental scores and to explore relationships between school-age motor and cognitive performance.Methods: Motor and cognitive performance was assessed in 29 previously cooled children at six to eight years using the Movement Assessment Battery for Children-2 (MABC-2) and the Wechsler Intelligence Scale for Children (WISC-IV). Associations between MABC-2 scores less than/equal (≤) 15th centile and perinatal factors, social/family background, 18-month Bayley-III scores and WISC-IV scores were explored.Results: Eleven of the 29 (38%) children had MABC-2 scores ≤15th centile including 7 (24%) ≤5th centile. No significant perinatal or socio-economic risk factors were identified. Motor scores <85 at 18 months failed to identify children with MABC-2 scores ≤15th centile. MABC-2 scores ≤15th centile were associated with lower Full Scale IQ (p = 0.045), Working Memory (p = 0.03) and Perceptual Reasoning (p = 0.005) scores at six to eight years and receiving greater support in school (p = 0.01).Conclusion: A third of cooled children without CP had MABC-2 scores indicating motor impairment at school age that was not identified at 18 months by Bayley-III. Most children with low MABC scores needed support at school. Sub-optimal MABC-2 scores indicate need for detailed school-age cognitive evaluation. [ABSTRACT FROM AUTHOR]

Aim: Concerns for infant destabilisation often prohibit parental holding of infants during therapeutic hypothermia (TH). We assessed the feasibility of maternal holding during TH, as the inability to hold can impede bonding.Methods: Vital signs were assessed in stable infants before, at two-minute intervals during and 30 minutes after a single 30-minute holding session. The infant remained on the blanket throughout holding, and both infant and blanket were placed into the mother's arms on top of a thin foam insulating barrier. Mothers and nurses were surveyed about their experience.Results: Ten infants undergoing TH for neonatal encephalopathy had no equipment malfunctions or dislodgement. The mean temperature was 33.4°C prior to and 33.5°C (p = 0.18) after holding. There was no significant bradycardia (heart rate <80 beats per minute), hypotension (mean arterial pressure <40 mm Hg) or oxygen desaturation (<93%). Nurses either strongly agreed (75%) or agreed (25%) with the statement 'After assisting with the holding protocol, I feel that holding during cooling is safe'. Mothers (100%) strongly agreed that other parents would benefit from holding.Conclusion: In a small sample of ten stable infants treated with TH for neonatal encephalopathy, holding resulted in no adverse events and positive feedback from mothers and nurses. [ABSTRACT FROM AUTHOR]

The use of minimal enteral nutrition (MEN) in newborns with hypoxic-ischaemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) represents a much-debated topic in neonatology. Currently, a large retrospective observational study is being undertaken to determine the optimum enteral and parenteral nutrition strategy for HIE newborns during TH.5 These data may provide the desired evidence to guide clinicians on the best feeding strategy in HIE. Whether these reassuring data were due to a selection bias (less severe/not critical HIE infants are more likely to be fed) or to a protective effect of early feeding is not known and should be addressed properly. [Extracted from the article]

Cognitive and behavioural outcomes: are they impaired in children without cerebral palsy following neonatal hypoxic-ischaemic encephalopathy? Schreglmann and colleagues report in this issue of Acta Paediatrica a systematic review of long-term cognitive and behavioural outcomes of neonatal hypoxic-ischaemic encephalopathy (HIE) in children without cerebral palsy (CP). Attention and executive function, and memory and learning domain scores were significantly lower in the moderate encephalopathy group compared to the mild encephalopathy group, and severe encephalopathy group compared to the moderate encephalopathy group. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

EBNEO commentary: Should we abandon therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries? Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh. Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh. [Extracted from the article]

5 Terrin G, Passariello A, Canani RB, Manguso F, Paludetto R, Cascioli C. Minimal enteral feeding reduces the risk of sepsis in feed-intolerant very low birth weight newborns. Is enteral feeding safe during therapeutic hypothermia in neonates with hypoxic-ischaemic encephalopathy? Traditionally, enteral feeds were withheld to reduce the risk of necrotising enterocolitis (NEC) in HIE babies who may have experienced intestinal hypoperfusion.1 However, growing evidence suggests that enteral nutrition is beneficial and promotes gut stimulation and feeding tolerance.2 Current evidence examining the safety of enteral feeds during TH is limited to two small retrospective studies. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Unlabelled: A systematic review and meta-analysis were performed to determine the effect of therapeutic hypothermia using low-technology methods, in settings with facilities for intensive care, in term or near-term infants with hypoxic-ischaemic encephalopathy on mortality, neurological morbidity at discharge and neurological morbidity at 6-24 months.Conclusion: Meta-analysis of three randomised controlled studies showed that low-technology therapeutic hypothermia in an intensive care setting significantly reduced the mortality and the neurological morbidity in survivors at discharge. [ABSTRACT FROM AUTHOR]

Aim: This was a clinical observational trial on a laminar flow device that provides total body hypothermia for infants with hypoxic ischaemic encephalopathy (HIE).Methods: We enrolled infants born at up to 35 weeks of gestation, who presented with HIE within six hours of birth. Total body cooling was achieved using the neonatal laminar flow unit for 72 hours, with continuous rectal temperature servo control, isolation and humidification. Outcome measures were cerebral palsy, a Bayley II Mental Development Index score <70, hearing loss or blindness. We compared findings with previously published studies.Results: We included 26 newborn infants (69% male) with a birthweight of 3.341 ± 1658 g and gestational age of 38.2 ± 3.2 weeks. The majority (62.6%) had a Sarnat HIE score of three and 38.4% had a score of two. Total body cooling (33-34°C) was achieved in 70 minutes and maintained with servo control, showing very little variability until rewarming. At 18-24 months of age, two of the 18 survivors were diagnosed with cerebral palsy and one was diagnosed with impaired hearing.Conclusion: The laminar flow unit proved effective in maintaining moderate total body hypothermia under well-controlled conditions, and our results were very similar to other studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim To investigate the effect of the therapeutic hypothermia ( TH), used in infants with moderate or severe hypoxic-ischaemic encephalopathy ( HIE), on fluid balance and incidence of hyponatremia. Methods Retrospective cohort study of moderate and severe HIE infants before (pre) and after (post) TH implementation. Daily fluid and electrolytes intake/output were collected from the medical records of each patient from day 1 to day 4 of life. Hyponatremia was defined as sodium <130 mEq/L. Results A total of 67 infants were studied: pre- TH = 29 and post- TH = 38. Infants in the post- TH group had greater weight gain [140 g (62, 227) vs. 10 g (−100, 105) p < 0.001] and lower serum sodium (130.9 ± 4.5 mmol/L vs. 133.4 ± 5.7, p = 0.008). The incidence of hyponatremia increased from 48 to 76% (p = 0.02). Conclusion In our centre, the implementation of TH was followed by an increased fluid retention and higher incidence of hyponatremia. Centres adopting TH should have clear guidelines for fluid and electrolyte management. [ABSTRACT FROM AUTHOR]

Aim To determine whether hypothermia alters the discriminative ability of postnatal nucleated red blood cells ( NRBCs) to distinguish between mild and moderate/severely encephalopathic infants. Methods A prospective cohort study recruited full-term neonates with hypoxic ischaemic encephalopathy ( HIE) from 2003 to 2012 (prehypothermic and hypothermic eras). The NRBC count was analysed in the first 24 h in all infants and compared between normothermic and hypothermic cohorts. The severity of encephalopathy was categorized using both clinical Sarnat score and continuous multichannel EEG. Results Eighty-six infants with HIE were included: in the normothermic group, 19 were clinically mild, 24 moderate/severe; in the hypothermic group, 22 were mild, 21 moderate/severe encephalopathy. NRBC count discriminated between mild and moderate/severe Sarnat scores in the normothermic group (p = 0.03) but not in the hypothermic group (p = 0.9). This change was due to a decrease in NRBCs among moderately encephalopathic infants in the hypothermic cohort. Conclusion Postnatal NRBCs distinguished between mild and moderate/severe encephalopathy in normothermic infants but not in infants undergoing therapeutic hypothermia. We advise caution when using postnatal blood samples to study diagnostic biomarkers for HIE without first analysing the potential impact of hypothermia upon these markers. [ABSTRACT FROM AUTHOR]

Background: Therapeutic hypothermia is now recommended as a standard of care for neonatal encephalopathy. Although adherence to standard cooling protocols used in the phase-III trials is essential, empiric approaches have prevailed in Japan. Aim: To elucidate the gap between the standard cooling methods and the current practice in Japan. Method: In July 2010, a questionnaire regarding the practice of neonatal encephalopathy was mailed to clinical leads of registered neonatal intensive care units. Result: 56.2% of the units were incapable of offering therapeutic hypothermia because of the reasons such as the shortage of human/medical resources (85.1%) and limited number of cases (21.1%). Eighty-nine centres provided therapeutic hypothermia using either selective-head cooling (88.8%) or whole-body cooling (11.2%). Various target temperatures and cooling durations were used; 20.2% of the units cooled infants without using purpose-built equipments, whereas 14.6% did not continuously monitor the body temperature. Discussion: Only 43.8% of the units provided therapeutic hypothermia. Even in centres where hypothermia was offered, adherence to the standard protocols was extremely poor. To secure the safety and efficacy, further promotion of the standard cooling protocols is required; an efficient cooling centre network has to be established by optimizing the work forth distribution and transportation system. [ABSTRACT FROM AUTHOR]

Background: Induced moderate hypothermia (HT) for 72 h has been shown to reduce the combined outcome of death or severe neurodevelopmental disabilities in asphyxiated full-term infants. A pathological amplitude integrated EEG background as early as 3–6 h after birth, has been shown to correlate to poor prognosis. Aim: The aim of this study was to investigate the correlation between amplitude integrated EEG during HT treatment and short-term outcome in asphyxiated full-term infants with moderate/severe hypoxic-ischaemic encephalopathy. Methods: Between December 2006 and December 2007, 24 infants were treated with moderate HT (33.5°C for 72 h) using a cooling mattress. Motor functions were assessed at 4 and 12 months of age. Results: Of the total birth cohort of 28,837 infants, 26 infants fulfilled the criteria for HT treatment (0.9/1000) of whom 23 was treated with HT and all of these infants had available amplitude integrated EEG data. Normal 1-year outcome was found in 10/15 infants with severely abnormal burst-suppression pattern or worse at 6 h of age. Severe abnormalities were found to be significantly predictive for abnormal outcome after 36 h. Conclusion: Among asphyxiated infants treated with HT, only those who had aEEG abnormalities persisting at and beyond 24 h after birth showed poor neurological outcome at 1 year. [ABSTRACT FROM AUTHOR]

Background: Induced mild hypothermia is an emerging therapy that has been shown to reduce the combined outcome of death or severe neurodevelopmental disabilities in asphyxiated full-term infants if started within 6 h after birth. Aim: To study the feasibility and safety of inducing hypothermia in asphyxiated infants already at the referring hospital by stopping active warming. Methods: Temperatures during passive induction of hypothermia were prospectively collected from transported asphyxiated infants. Results: Between December 2006 and April 2008, 37 infants of the total birth cohort of 40 350 fulfilled the criteria for hypothermia treatment. Eighteen of 34 infants treated with induced hypothermia were outborn. The rectal temperatures of the infants were 33.0–36.4°C before transport and 31.0–36.5°C on arrival. Six of the infants had a sub-therapeutic (<33.0°C) rectal temperature on arrival. Conclusion: Passive induction of hypothermia by turning off active warming devices is possible, making an earlier start of hypothermia achievable. However, there is a substantial risk of unintended excessive cooling; therefore, continuous monitoring of the central temperature is mandatory when such a strategy is used. [ABSTRACT FROM AUTHOR]

Background: The 2007 Cochrane review of therapeutic hypothermia for neonatal encephalopathy (NE) indicates a significant reduction in adverse outcome. UK National Institute for Clinical Excellence guidelines are awaited. Objective: To benchmark current opinion and practice to inform future strategies for optimal knowledge transfer for therapeutic hypothermia. Methods: A web based questionnaire (30 sections related to opinion and practice of management of NE) sent to the clinical leads of Level I, II and III neonatal units throughout the UK in November/December 2007. Results: One hundred and twenty-five (out of 195) UK neonatal units responded (response rate 66%). Ten percent, 37.5% and 51.5% responses were from level I, II and III units respectively. Twenty eight percent of all units provided therapeutic hypothermia locally (52% of level III units), however 80% of responders would offer therapeutic hypothermia if there was the facility. Overall, 57% of responders considered therapeutic hypothermia effective or very effective – similar for all unit levels; 43% considered more data are required. Regional availability of therapeutic hypothermia exists in 55% of units and 41% of units offer transfer to a regional centre for therapeutic hypothermia. Conclusion: In the UK in 2007, access to therapeutic hypothermia was widespread although not universal. More than half of responders considered therapeutic hypothermia effective. Fifty-five percent of perinatal networks have the facility to offer therapeutic hypothermia. The involvement of national bodies may be necessary to ensure the adoption of therapeutic hypothermia according to defined protocols and standards; registration is important and will help ensure universal neurodevelopmental follow up. [ABSTRACT FROM AUTHOR]

Does topiramate in addition to therapeutic hypothermia reduce seizure burden in infants with hypoxic-ischaemic encephalopathy compared to therapeutic hypothermia alone? Therapeutic hypothermia decreases mortality and improves neurodevelopmental outcomes in infants with moderate to severe hypoxic-ischaemic encephalopathy.[[1], [3]] However, as morbidity in HIE remains high, adjuvant therapies that further improve outcomes are needed. The authors found no statistically significant difference in prevalence of seizures at any of the time frames measured between those who received topiramate and those who did not, however, overall seizure prevalence for the entire study time was not presented. [Extracted from the article]

Therapeutic hypothermia (TH) has become the standard neuroprotective intervention for newborn infants with hypoxic-ischaemic encephalopathy (HIE) and it is recommended in resuscitation guidelines.[1] Adequate analgesia and sedation is fundamental to maximise the efficacy of TH. Our aim was to analyse data on current analgesia and sedation practices during TH in neonatal intensive care units (NICUs) in Italy, using a web-based questionnaire with 19 closed questions. The questionnaire investigated NICU characteristics and the type of TH, namely total body versus selective TH and the analgesia and sedation policies used during TH. [Extracted from the article]

Coeliac disease is a chronic immune-mediated disorder that affects the small intestine, and it occurs in genetically sensitive individuals exposed to gluten. At least three papers[[10]] published in 2019 stated that the quantity of gluten intake plays an important role in the risk of coeliac disease. Association of gluten intake during the first 5 years of life with incidence of celiac disease autoimmunity and celiac disease among children at increased risk. [Extracted from the article]

Standardised treatment protocols and treatment guidelines might help clinicians to treat newborn infants with this relatively rare condition and answer many of those questions. The questions also covered sedation and anticonvulsant treatment during cooling, imaging during and after cooling and neonatal follow-ups. [Extracted from the article]

A correction to the article "Major concerns about late hypothermia study" by Walløe L., Hjort N.L., and Thoresen M. that was published in a 2019 issue is presented.

The article discusses cooling during hypothermia treatment, perinatal asphyxia and long-term effects of the necessary sedative drugs used in newborn. Topics include parenteral nutrition, liver and kidney metabolism during cooling and opiates damage the immature brain including the cerebellum injuries.

The article discusses therapeutic hypothermia for infants diagnosed with hypoxia and ischaemia encephalopathy. Topics include randomised controlled trial of treatment in infants, neurodevelopment impairment of infants and investigation into other treatments or medications that may mitigate neurological injury.

The authors comment on an article focusing on the effectiveness of Erythropoietin (EPO) monotherapy in reducing mortality or disability in neonates with hypoxic ischaemic encephalopathy. Topics discussed include the comparison of EPO against placebo, without adjunctive therapeutic hypothermia (TH); the reduction in brain injury to neonates treated with EPO; and the lack of clinical data on the proven effectiveness of TH.

An introduction is presented in which the editor discusses a study on therapeutic hypothermia as treatment for newborn infants suffering from moderate to severe hypoxic-ischaemic neonatal encephalopathy, published within the issue.

A response from the author of the article "The Effect of the Implementation of Therapeutic Hypothermia on Fluid Balance and Incidence of Hyponatremia in Neonates With Moderate or Severe Hypoxic-Ischemic Encephalopathy" that was published in the 2013 issue is presented.

The author discusses a study regarding the early outcomes of infants with hypoxic-ischaemic encephalopathy (HIE) following the introduction of therapeutic hypothermia (TH) to the neonatal service in Western Cape, South Africa. Topics include the differences in the definiton of HIE between different resource settings that might impact the outcomes, the aetiology of HIE, and the prevalences of comorbidities.

A letter to the editor is presented in response to the article "The Effect of the Implementation of Therapeutic Hypothermia on Fluid Balance and Incidence of Hyponatremia in Neonates With Moderate or Severe Hypoxic-Ischemic Encephalopathy," in the 2013 issue.