Moderate Neonatal Encephalopathy Research Articles

Effect of gestational age on cerebral lesions in neonatal encephalopathy

ObjectiveTo determine the risk on brain lesions according to gestational age (GA) in neonates with neonatal encephalopathy.DesignSecondary analysis of the prospective national French population-based cohort, Long-Term Outcome of NeonataL EncePhALopathy.SettingFrench...

Feasibility and Safety of Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-01): A Randomized, Double-blind, Placebo-controlled Phase Ib Clinical Trial

To test feasibility and safety of administering sildenafil in neonates with neonatal encephalopathy (NE), developing brain injury despite therapeutic hypothermia (TH). We performed a randomized, double-blind, placebo-controlled phase Ib clinical trial between 2016 and 2019 in neonates with moderate or severe NE, displaying brain injury on day-2 magnetic resonance imaging (MRI) despite TH. Neonates were randomized (2:1) to 7-day sildenafil or placebo (2mg/kg/dose enterally every 12hours, 14 doses). Outcomes included feasibility and safety (primary outcomes), pharmacokinetics (secondary), and day-30 neuroimaging and 18-month neurodevelopment assessments (exploratory). Of the 24 enrolled neonates, 8 were randomized to sildenafil and 3 to placebo. A mild decrease in blood pressure was reported in 2 of the 8 neonates after initial dose, but not with subsequent doses. Sildenafil plasma steady-state concentration was rapidly reached, but decreased after TH discontinuation. Twelve percent of neonates (1/8) neonates died in the sildenafil group and 0% (0/3) in the placebo group. Among surviving neonates, partial recovery of injury, fewer cystic lesions, and less brain volume loss on day-30 magnetic resonance imaging were noted in 71% (5/7) of the sildenafil group and in 0% (0/3) of the placebo group. The rate of death or survival to 18 months with severe neurodevelopmental impairment was 57% (4/7) in the sildenafil group and 100% (3/3) in the placebo group. Sildenafil was safe and well-absorbed in neonates with NE treated with TH. Optimal dosing needs to be established. Evaluation of a larger number of neonates through subsequent phases II and III trials is required to establish efficacy. ClinicalTrials.govNCT02812433.

Amplitude-Integrated Electroencephalography Evolution and Magnetic Resonance Imaging Injury in Mild and Moderate to Severe Neonatal Encephalopathy.

This study aimed to describe the evolution of amplitude-integrated electroencephalography (aEEG) in neonatal encephalopathy (NE) during therapeutic hypothermia (TH) and evaluate the association between aEEG parameters and magnetic resonance imaging (MRI) injury. aEEG data of infants who underwent TH were reviewed for background, sleep wake cycling (SWC), and seizures. Conventional electroencephalography (cEEG) background was assessed from the reports. Discordance of background on aEEG and cEEG was defined if there was a difference in the severity of the background. MRI injury (total score ≥ 5) was assessed by using the Weeke scoring system. A total of 46 infants were included; 23 (50%) with mild NE and 23 (50%) with moderate to severe NE. Comparing mild NE with moderate to severe NE, the initial aEEG background differed with more mild being continuous (70 vs. 52%), with fewer being discontinuous (0 vs. 22%) and flat tracing (0 vs. 4%), whereas burst suppression (4 vs. 4%) and low voltage (26 vs. 18%) did not differ. There was a notably common discordance between the background assessment on cEEG with aEEG in 82% with continuous and 40% low voltage aEEG background. MRI abnormalities were identified in four infants with mild NE and seven infants with moderate to severe NE. MRI injury was associated with aEEG seizures in infants with moderate to severe NE. aEEG seizures are useful to predict MRI injury in moderate to severe NE infants. There is a large discrepancy between aEEG, cEEG, and MRI in neonates treated by TH. · MRI injury was identified in 29% of moderate NE infants and in 50% of severe NE infants.. · aEEG seizures were associated with MRI injury in the moderate to severe NE infants.. · MRI injury was identified in 16% infants with mild NE.. · Mild NE infants with normal aEEG were unlikely to have MRI injury.. · There was a large discrepancy between aEEG, cEEG, and MRI in infants treated by TH..

Evaluation of heterogeneity in effect of therapeutic hypothermia by sex among infants with neonatal encephalopathy.

Our objective was to examine heterogeneity in the effect of therapeutic hypothermia by sex in infants with moderate or severe neonatal encephalopathy. We conducted a post hoc analysis of the Induced Hypothermia trial, which included infants born at gestational ages ≥36 weeks, admitted at ≤6 postnatal hours with evidence of severe acidosis or perinatal complications and moderate or severe neonatal encephalopathy. Multivariate modified Poisson regression models were used to compare the treatment effect of whole-body hypothermia versus control, with an evaluation of interaction by sex, on the primary outcome of death or moderate or severe disability at 18-22 months of corrected age. A total of 101 infants (51 male, 50 female) were randomly assigned to hypothermia treatment and 104 infants (64 male, 40 female) to control. The primary outcome occurred in 45% of the hypothermia group and 63% of the control group (RR 0.73; 95% CI 0.56, 0.94). There was no significant difference (interaction P = 0.50) in the treatment effect of hypothermia on the primary outcome between females (RR 0.79; 95% CI 0.54, 1.17) compared to males (RR 0.63; 95% CI 0.44, 0.91). We found no evidence that sex influences the treatment effect of hypothermia in infants with moderate or severe neonatal encephalopathy. Preclinical evidence suggests a differential effect in response to cooling treatment of hypoxic-ischemic injury between males and females. We found no evidence of heterogeneity in the treatment effect of whole-body hypothermia by sex in this post hoc subgroup analysis of infants with moderate or severe neonatal encephalopathy from the National Institute of Child Health and Human Development Neonatal Research NetworkInduced Hypothermia trial.

Long-term consequences of neonatal encephalopathy in the hypothermia era: protocol for a follow-up cohort study at 9 years of age

IntroductionTherapeutic hypothermia (TH) became the standard of care treatment for neonates with moderate and severe neonatal encephalopathy (NE) in most industrialized countries about 10 years ago. Although TH is effective...

EBNEO Commentary: Safety and efficacy of erythropoietin in neonates with hypoxic-ischaemic encephalopathy.

EBNEO Commentary: Safety and efficacy of erythropoietin in neonates with hypoxic-ischaemic encephalopathy.

Variations in care of neonates during therapeutic hypothermia: call for care practice bundle implementation.

Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.

Efficacy of Magnesium Sulfate in Addition to Melatonin Therapy in Neonates With Hypoxic-Ischemic Encephalopathy.

Background: One of the most important causes of neonatal deaths in developing nations is birth asphyxia. Though the probability of a complete recovery is very low, hypoxic-ischemic encephalopathy (HIE) associated with asphyxia can be managed with multiple treatment options. The study evaluated the efficacy of the addition of magnesium sulfate (MgSO4) to melatonin therapy in neonates with HIE.Methodology: A prospective, observational study was conducted in the department of neonatal intensive care, Pakistan Institute of Medical Sciences Hospital, Islamabad, Pakistan from October 2020 to March 2021. All neonates with an Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score of less than five at five minutes, umbilical blood pH of less than 7.0, and moderate neonatal encephalopathy as detected on the modified Sarnat score which is a clinical tool used for the assessment of the severity of HIE were included in the study. Neonates with congenital abnormalities, intrauterine growth retardation, neonatal sepsis, and infants born to mothers with diabetes mellitus type 2 were excluded from the study. The infants were randomly assigned to either of the groups, i.e., i) group 1 included neonates who were administered at least three doses of magnesium sulfate (MgSO4) infusion in addition to melatonin, or ii) group 2 included neonates who were administered melatonin only. Blood samples of all neonates were evaluated and compared between the two groups.Results: A total of 90 neonates with HIE were included in the study. There was a predominance of female neonates. The mean ages of babies in group 1 and group 2 were 37.2 ± 0.43 and 37.3 ± 0.59 weeks, respectively. The mean weight on the term was 2.88 ± 0.11 and 2.89 ± 0.10, respectively. The Apgar score at 5 mins in group 1 was 1.73 ± 0.81 while in group 2, 1.82 ± 0.94. It was found that there was a more significant improvement in pH after 3 days and after one week of treatment in group 1 as compared to group 2. The mean pH in babies after three days of intervention was 7.23 ± 0.03 in group 1 which was significantly better than group 2 (p<0.0001). After seven days, the mean normalized to 7.39 ± 0.04 in group 1 (p < 0.0001). It was found that in patients in group 1, the mortality was lower than in group 2 (p < 0.0001).Conclusion: HIE patients who were administered melatonin in combination with magnesium sulfate yielded better patient outcomes. Thus, it was concluded that the use of magnesium sulfate as dual therapy with melatonin improved patient outcomes for HIE. However, it is recommended that similar studies are conducted with a wider range of parameters, such as duration of hospital stay and assessment of the neurological outcomes of the patients.

Differences in standardized neonatal encephalopathy exam criteria may impact therapeutic hypothermia eligibility.

Therapeutic hypothermia (TH) is routinely provided to those with moderate or severe neonatal encephalopathy (NE). Subtle differences exist in the standardized exams used to define NE severity. We aimed to assess if an infant's TH eligibility status differed if they were evaluated using either the NICHD/Neonatal Research Network's (NICHD-NRN) or TOBY/British Association of Perinatal Medicine's (TOBY-BAPM) neurological exam. Encephalopathic infants ≥36 weeks with evidence of perinatal asphyxia and complete documentation of the neurological exam &lt;6 h of age were included. TH eligibility using the NICHD-NRN and TOBY-BAPM criteria was determined based upon the documented exams. Ninety-one encephalopathic infants were included. Despite good agreement between the two exams (κ = 0.715, p &lt; 0.001), TH eligibility differed between them (p &lt; 0.001). A total of 47 infants were deemed eligible by at least one method-46 using NICHD-NRN and 35 using TOBY-BAPM. Of the 12 infants eligible per NICHD-NRN, but ineligible per TOBY-BAPM, two developed electrographic seizures and seven demonstrated hypoxic-ischemic cerebral injury. Both the NICHD-NRN and TOBY-BAPM exams are evidence-based. Despite this, there is a significant difference in the number of infants eligible for TH depending on which exam is used. The NICHD-NRN exam identifies a greater proportion as eligible. There are subtle differences in the NICHD-NRN and TOBY-BAPM's encephalopathy exams used to determine eligibility for TH. This results in a significant difference in the proportion of infants determined to be eligible for TH depending on which encephalopathy exam is used. The NICHD-NRN encephalopathy exam identifies more infants as being eligible for TH than the TOBY-BAPM encephalopathy exam. This may result in different rates of cooling depending on which evidence-based neurological exam for evaluation of encephalopathy a center uses.

Comparison of numerical and standard sarnat grading using the NICHD and SIBEN methods

ObjectiveThe NICHD and SIBEN assessments are adapted from the Sarnat grade, and used to determine severity of neonatal encephalopathy (NE). We compare NICHD and SIBEN methods, and their ability to define a minimum threshold associated with significant cerebral injury.Study designBetween 2016 and 2019, 145 infants with NE (77-mild; 65-moderate; 3-severe) were included. NICHD and SIBEN grade and numerical scores were assigned. Kappa scores described agreement between methods, and ROC curves their ability to predict MR injury.ResultsGood agreement existed between grading systems (K = 0.86). SIBEN defined more infants as moderate, and less as mild, than NICHD (p < 0.001). Both numerical scores were superior to standard grades in predicting MR injury.ConclusionDespite good agreement between methods, SIBEN defines more infants as moderate NE. Both numerical scores were superior to standard grade, and comparable to each other, in defining a minimum threshold for cerebral injury. Further assessment contrasting their predictive ability for long-term outcome is required.

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

SummaryBackgroundAlthough therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia.MethodsWe did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385.FindingsWe screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention.InterpretationTherapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available.FundingNational Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation.TranslationsFor the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.

Noninvasive monitoring of evolving urinary metabolic patterns in neonatal encephalopathy.

Infants with moderate and severe neonatal encephalopathy (NE) frequently suffer from long-term adverse outcomes. We hypothesize that the urinary metabolome of newborns with NE reflects the evolution of injury patterns observed with magnetic resonance imaging (MRI). Eligible patients were newborn infants with perinatal asphyxia evolving to NE and qualifying for therapeutic hypothermia (TH) included in the HYPOTOP trial. MRI was employed for characterizing brain injury. Urine samples of 55 infants were collected before, during, and after TH. Metabolic profiles of samples were recorded employing three complementary mass spectrometry-based assays, and the alteration of detected metabolic features between groups was assessed. The longitudinal assessment revealed significant perturbations of the urinary metabolome. After 24 h of TH, a stable disease pattern evolved characterized by the alterations of 4-8% of metabolic features related to lipid metabolism, metabolism of cofactors and vitamins, glycan biosynthesis and metabolism, amino acid metabolism, and nucleotide metabolism. Characteristic metabolomic fingerprints were observed for different MRI injury patterns. This study shows the potential of urinary metabolic profiles for the noninvasive monitoring of brain injury of infants with NE during TH. A comprehensive approach for the study of the urinary metabolome was employed involving a semi-targeted capillary electrophoresis-time-of-flight mass spectrometry (TOFMS) assay, an untargeted ultra-performance liquid chromatography (UPLC)-quadrupole TOFMS assay, and a targeted UPLC-tandem MS-based method for the quantification of amino acids. The longitudinal study of the urinary metabolome identified dynamic metabolic changes between birth and until 96 h after the initiation of TH. The identification of altered metabolic pathways in newborns with pathologic MRI outcomes might offer the possibility of developing noninvasive monitoring approaches for personalized adjustment of the treatment and for supporting early outcome prediction.

Development, Reliability, and Testing of a New Rating Scale for Neonatal Encephalopathy

To develop and test the Neonatal Encephalopathy-Rating Scale (NE-RS), a new rating scale to grade the severity of neonatal encephalopathy (NE) within the first 6hours after birth. A 3-phase process was conducted: (1) design of a comprehensive scale that would be specific, sensitive, brief, and unsophisticated; (2) evaluation in a cohort of infants with neonatal encephalopathy and healthy controls; and (3) validation with brain magnetic resonance imaging findings and outcome at 2years of age. We evaluated the NE-RS in 54 infants with NE and 28 healthy infants. The NE-RS had excellent internal consistency (Cronbach alpha coefficient: 0.93 [95% CI 0.86-0.94]) and reliability (intraclass correlation coefficient in the NE cohort 0.996 [95% CI 0.993-0.998; P<.001]). Alertness, posture, motor response, and spontaneous activity were the top discriminators for degrees of NE. The cut-off value for mild vs moderate NE was 8 points (area under the curve [AUC] 0.99, 95% CI 0.85-1.00) and for moderate vs severe NE, 30 points (AUC 0.93, 95% CI 0.81-0.99). The NE-RS was significantly correlated with the magnetic resonance imaging score (Spearman Rho 0.77, P<.001) and discriminated infants who had an adverse outcome (AUC 0.91, 95% CI 0.83-0.99, sensitivity 0.82, specificity 0.81, positive predictive value 0.87, negative predictive value 0.74). The NE-RS is reliable and performs well in reflecting the severity of NE within the first 6hours after birth. This tool could be useful when assessing clinical criteria for therapeutic hypothermia in NE.

Shoulder dystocia, umbilical cord blood gases and neonatal encephalopathy

The interpretation of umbilical cord gases may not be straightforward following shoulder dystocia. We reviewed Perinatal and Maternal Mortality Review Committee data from New Zealand infants with moderate and severe neonatal encephalopathy (NE) for 2010-2017 inclusive. If one or more of: pH of ≤7.1; base excess of ≤-12mmol/L; or lactate of ≥6mmol/L were present it was considered an abnormal result. One-third (12/36) of infants born following shoulder dystocia had documented umbilical cord gases within the normal range. It is important for clinicians to be aware of this possibility when assessing newborn infants with NE.

Reduced white-matter integrity and lower speed of information processing in adolescents with mild and moderate neonatal hypoxic-ischaemic encephalopathy.

Studies have shown that adolescents with moderate hypoxic-ischaemic encephalopathy (HIE) may have specific cognitive deficits, especially reduced speed of information processing. The aim of our study was to confirm these earlier findings find out whether the degree of impairment in speed of information processing correlates with the degree of white-matter impairment as measured by diffusion tensor imaging (DTI). Thirty-three participants (mean age 18y 5mo, SD 12mo; 19 male) with mild or moderate HIE and 32 neurotypical adolescents (mean age 17y 10mo, SD 12mo, 18 male) completed a comprehensive neuropsychological battery measuring short-term memory, inhibition, speed of information processing, long-term visual and verbal memory. Fourteen participants also underwent structural MRI and DTI scans. After controlling for age, gender and maternal education we found a significant effect of HIE on speed of information processing (F(2, 64)=3.51, p<.037, η2=0.115), but not on other neuropsychological domains. Using tract-based spatial statistics we were also able to confirm a correlation between the degree of impairment in this cognitive domain and fractional anisotropy in several white-matter tracts. The long-term cognitive outcome of moderate HIE includes reduced speed of information processing and is in part mediated by reduced integrity of major white-matter tracts.

System Specific Effects of Therapeutic Hypothermia with Neonatal Encephalopathy: Pearls for Clinicians.

Neonatal encephalopathy (NE) is defined as a condition of impaired neurological function often caused by a peripartum event that impairs gas exchange resulting in hypoxia, hypercapnia, cerebral ischemia, and metabolic acidosis. NE is a significant cause of neonatal morbidity and mortality. Therapeutic hypothermia (TH) is the standard of care for the treatment of moderate and severe NE and has significantly improved long-term outcomes for affected infants. There are extensive systemic physiologic effects associated with TH that clinicians need to be aware of to optimize care for these infants. There is a paucity of literature that comprehensively identifies causal relationships between the physiologic and biochemical effects of TH. This can leave neonatal clinicians devoid of a comprehensive understanding of the medical management of NE. Therefore, this article seeks to help fill this gap, improve clinician knowledge base, and ultimately improve the care of infants undergoing TH.

Is there a role for therapeutic hypothermia administration in term infants with mild neonatal encephalopathy?

Identifying term infants presenting with early mild neonatal encephalopathy (NE) as candidates for therapeutic hypothermia (TH) remains unclear. Study objectives were to characterize the neonatal clinical, magnetic resonance imaging (MRI), and longer-term outcome in infants with mild NE treated with TH. Retrospective cohort study of infants admitted with mild or moderate NE treated with TH. Enrollment criteria included a sentinel event, severe acidosis, DR interventions, and low Apgar scores. Infants with mild (n = 11) and moderate NE (n = 37) received TH. Mild NE findings included hyperalertness (64%), hypotonia (73%), high level sensory response (91%); 64% progressed to moderate NE. Infants with mild vs. moderate NE had less severe MRI changes (0 vs. 16%) and no cerebral palsy (CP) (0 vs. 13%). Outcomes were favorable with mild NE whereas four infants with moderate NE developed CP. A potential role for TH in this population requires further study.

Hospital-related, maternal, and fetal risk factors for neonatal asphyxia and moderate or severe hypoxic-ischemic encephalopathy: a retrospective cohort study

Aim A previous large US study had documented an increased risk of asphyxia in small volume and rural hospitals. Our objective was to evaluate this in all hospitals in Alberta, a Canadian province. Methods Retrospective cohort study of all singleton births ≥ 35-week gestation, in Alberta, from 2002–16 recorded in a perinatal database. Asphyxia was defined as intrapartum stillbirth or neonatal death from asphyxia or Neonatal Intensive Care Unit admission and at least two of the following: a. Apgar score of ≤ 5 at 10 minutes; b. mechanical ventilation or chest compressions for resuscitation within 10 minutes; c. cord pH < 7.00 (venous or arterial), or arterial base excess ≥ 12 at birth. Urban hospitals were defined as those serving a population of ≥ 50 000. Hospital volume was categorized by the following: urban: < 1200, 1200–2399, 2400–3600, > 3600 annual births and Rural: < 50, 50–599, 600–1699 annual births. Data on moderate–severe neonatal hypoxic-ischemic encephalopathy was also obtained from two provincial asphyxia databases for 2010–2016. Results The overall rate of neonatal asphyxia was 2.28 per 1000 births for the study period and was 2.5/1000 in the urban hospitals and 1.35/1000 in the rural hospitals, OR: 1.86 95% CI (1.58, 2.19). The rate of moderate or severe neonatal hypoxic-ischemic encephalopathy was 0.9/1000 and was not associated with urban hospital birth; OR: 1.12 95%CI (0.82, 1.53) hospital volume was also not associated with asphyxia or moderate or severe neonatal hypoxic-ischemic encephalopathy. Conclusions This study observed similar rates of asphyxia and moderate or severe neonatal hypoxic-ischemic encephalopathy for rural and urban hospitals in Alberta and no association with hospital volume.

Hypoxia-Ischemia and Hypothermia Independently and Interactively Affect Neuronal Pathology in Neonatal Piglets with Short-Term Recovery

Therapeutic hypothermia is the standard of clinical care for moderate neonatal hypoxic-ischemic encephalopathy. We investigated the independent and interactive effects of hypoxia-ischemia (HI) and temperature on neuronal survival and injury in basal ganglia and cerebral cortex in neonatal piglets. Male piglets were randomized to receive HI injury or sham procedure followed by 29 h of normothermia, sustained hypothermia induced at 2 h, or hypothermia with rewarming during fentanyl-nitrous oxide anesthesia. Viable and injured neurons and apoptotic profiles were counted in the anterior putamen, posterior putamen, and motor cortex at 29 h after HI injury or sham procedure. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) identified genomic DNA fragmentation to confirm cell death. Though hypothermia after HI preserved viable neurons in the anterior and posterior putamen, hypothermia prevented neuronal injury in only the anterior putamen. Hypothermia initiated 2 h after injury did not protect against apoptotic cell death in either the putamen or motor cortex, and rewarming from hypothermia was associated with increased apoptosis in the motor cortex. In non-HI shams, sustained hypothermia during anesthesia was associated with neuronal injury and corresponding viable neuron loss in the anterior putamen and motor cortex. TUNEL confirmed increased neurodegeneration in the putamen of hypothermic shams. Anesthetized, normothermic shams did not show abnormal neuronal cytopathology in the putamen or motor cortex, thereby demonstrating minimal contribution of the anesthetic regimen to neuronal injury during normothermia. We conclude that the efficacy of hypothermic protection after HI is region specific and that hypothermia during anesthesia in the absence of HI may be associated with neuronal injury in the developing brain. Studies examining the potential interactions between hypothermia and anesthesia, as well as with longer durations of hypothermia, are needed.

Contributory factors and potentially avoidable neonatal encephalopathy associated with acute peripartum events: An observational study

In 25% of affected babies, neonatal encephalopathy results from acute peripartum events, but rigorous review of these cases for quality improvement is seldom reported. New Zealand has maintained a national database of all babies diagnosed with Sarnat moderate and severe neonatal encephalopathy since 2010 under the Perinatal and Maternal Mortality Review Committee. To determine the rate of contributory factors, potentially avoidable mortality or morbidity, and to identify key areas for improvements to maternity and neonatal care among cases of neonatal encephalopathy following an acute peripartum event. Sarnat moderate and severe cases identified from the national collection of neonatal encephalopathy with a history of an acute peripartum event were reviewed using a standardised independent multidisciplinary methodology and a tool for assessing contributory factors and potential avoidability, with the addition of a human factors lens. Forty-seven cases from 2013 to 2015 were reviewed. The most common acute peripartum events were placental abruption (12) and shoulder dystocia (11). Contributory factors were identified in 89%, and the severity of outcome was potentially avoidable in 66%. Key modifiable areas included dynamic risk assessment, preparedness for obstetric and neonatal emergencies, best practice for maternal and fetal surveillance in labour, and documentation. There is significant potential to improve quality and safety in acute peripartum care to reduce the risk of neonatal encephalopathy. Human factors were not well captured by the clinical notes or review tool. Attention to human factors by improved methodology can enhance review of neonatal encephalopathy.