Moderate Hypoxic-ischemic Encephalopathy Research Articles

Clinical Characteristics and Risk Factors of Neonatal Hypoxic-Ischaemic Encephalopathy and Its Associated Neurodevelopmental Outcomes During the First Two Years of Life: A Retrospective Study in Saudi Arabia.

This study aimed to determine the clinical characteristics and factors associated with neonatal hypoxic-ischaemic encephalopathy (HIE) and its neurodevelopmental outcomes. We conductedretrospective case-control researchto investigate the clinical and labour-related risk factors for HIE. In addition, a single-centre cohort study was conducted on infants with HIE to describe their neurodevelopment from birth to 24 months. For this investigation, cases with a diagnosis of HIE who were born at King Abdullah Children's Specialist Hospital (KASCH), Riyadh, Saudi Arabia, between 2015 and 2019 were identified and matched with controls from the same facility (1:4). Each case's clinical information was extracted using electronic medical records. In addition,24-monthfollow-up HIE cases were included in a cohort study to describe their neurodevelopmental outcomes. The sample includes 60 infants diagnosed with HIE and 234 infants serving as controls, with a mean gestational age of 38.8 weeks (SD 1.6)and a predominance of males (56.4%). Around one-thirdof the HIE cases (36.6%) had moderate HIE (stage 2), whereas 35.1% of infants had severe HIE (stage 3), according to Sarnat staging. Compared to the control group, children with HIE were twice as likely to be born to mothers with maternal comorbidities and more likely to have prepartum and intrapartum complications. A 24-month follow-up of neurodevelopmental outcomes for HIE babies revealed that approximately 24% exhibited delays in gross motor skill development, 22% in fine motor skill development, 33% in language skill development, and 22% in social skill development. In the HIE group, maternal comorbidities and prepartumor intrapartum complications were more common. The severity grade of HIE can be used to predict neurodevelopmental consequences. Enhancing patient care and rehabilitation requires a minimum of 24 months of neurodevelopmental follow-up.

Hypothermia for neonatal hypoxic–ischemic encephalopathy: Retrospective descriptive study of features associated with poor outcome

AimTo investigate the clinical, laboratory, electrophysiological, and imaging features associated with death or neurological impairment at 1 year of age in term neonates with hypoxic–ischemic encephalopathy (HIE) treated by therapeutic hypothermia (TH). MethodsThis was a single-center retrospective and descriptive study conducted over a period of 2 years. We included consecutive term newborns with moderate or severe HIE who were treated by TH initiated within the sixth hour after birth and continued for 72 h,. For all patients, brain magnetic resonance imaging (MRI) was performed before the eighth day and a score was established; furthermore, at least two electroencephalograms were recorded. ResultsAmong the 33 patients included, 20 neonates had a favorable outcome and 13 had an unfavorable outcome. Early clinical seizures (15% vs. 53.8%, p = 0.047), the persistence of a poor prognosis according to the electroencephalogram pattern after TH (0% vs. 69.2%, p = 0.0001), and an elevated score on the early brain MRI (2 vs. 11, p < 0.001) combined with a high lactate/N-acetyl-aspartate ratio (0.52 vs. 1.33, p = 0.008) on spectroscopy were associated with death and a poor outcome. ConclusionA combination of tools can help the medical team to establish the most reliable prognosis for these full-term neonates, to guide care, and to inform parents most appropriately and sincerely.

Evolution of swallowing and feeding abilities of neonates with hypoxic-ischaemic encephalopathy during hospitalisation: A case series

Purpose To describe the evolution of swallowing and feeding abilities of neonates with hypoxic-ischaemic encephalopathy (HIE) during hospitalisation. Method A longitudinal cohort study was used. Twenty-nine participants (median age 39.0 weeks [IQR = 2.0 weeks]) with mild (n = 7), moderate (n = 19) and severe (n = 3) HIE were included. Clinical swallowing and feeding assessments were conducted at introduction of oral feeds and at discharge using the Neonatal Feeding Assessment Scale (NFAS). Videofluoroscopic swallow studies (VFSS) supplemented the NFAS before discharge. Result Approximately two thirds of participants showed symptoms of oropharyngeal dysphagia (OPD) during initial NFAS and VFSS. Significantly fewer OPD symptoms occurred at discharge NFAS (p = 0.004). Endurance during non-nutritive sucking (p < 0.001) and nutritive sucking (p < 0.001) significantly improved. Nine participants (31.0%) demonstrated penetration or aspiration. Most aspiration events were silent (60%). Instrumental assessment identified pharyngeal phase dysphagia more effectively than bedside evaluation. High proportions of participants displayed OPD symptoms regardless of HIE severity. The correlation between OPD severity and the length of hospitalisation (p = 0.052) was not significant. Conclusion All grades of HIE should be considered for early intervention by speech-language pathologists before discharge. Findings may be valuable to neonatal feeding teams.

Maternal and neonatal exposure to risk factors for neonates with moderate or severe hypoxic ischemic encephalopathy: a cross-sectional study

BackgroundTo investigate the association between maternal and neonatal exposure to the relevant influencing factors and risk of moderate or severe hypoxic ischemic encephalopathy (HIE), and the possible interactions in the Chinese population.MethodsA cross-sectional study comprising 228 neonates from Henan Children’s Hospital during the five-year period 2015–2020 in China was conducted. All neonatal basic demographic information and clinical records were documented from the neonatal HIE database. Comparisons between mild HIE and moderate or severe HIE were conducted with the t-test or Wilcoxon rank-sum test for continuous variables and the Chi-square test for categorical variables. Unconditional multiple logistic regression models were used to generate the odds ratios(ORs) and 95% confidence intervals(CIs). In addition, we also used an additive model to test for possible biological interactions among the factors.ResultsOf the 228 neonates, the males had a statistically significantly higher frequency compared with the females between the two groups (P = 0.030). Trend analysis results found that with the decreased of the neonatal birth weight, the detection rates of moderate or severe HIE in males and females were gradually increased (Ptrend < 0.05). The detection of moderate or severe HIE in males and females increased with the decreased of neonatal gestational age at birth(Ptrend < 0.05). However, no interaction was detected between neonatal birth weight and gestational age at birth based on the additive model, the Relative Excess Risk of Interaction and 95% CI was 0.821(-0.046,1.687). The adjusted multiple logistic regression model showed that low birth weight(ORadj:1.965, 95%CI:1.086–4.127),premature infant(ORadj:1.557, 95%CI:1.589–4.862),1-min Apgar’s score < 7(ORadj:5.618, 95%CI:3.724–7.353),intrauterine distress(ORadj:4.916, 95%CI:3.431–7.398),amniotic fluid contamination (ORadj:3.965, 95%CI:2.153–5.782) significantly increased the risk of neonatal moderate or severe HIE.ConclusionNeonates with low birth weight, premature infant,1-min Apgar’s score < 7, intrauterine distress, amniotic fluid contamination are risk factors for moderate or severe HIE. Notably, we found no biological interaction between risk factors based on the additive model, these findings may help to inform prevention strategies, as this may effectively reduce the incidence of neonatal moderate or severe HIE.

Risk factors for hypoxic-ischemic encephalopathy or neonatal death in placental abruption

ObjectiveTo identify risk factors for moderate or severe hypoxic-ischemic encephalopathy (HIE), or neonatal death in clinical placental abruption. Material and methodsA nested case-control study within a cohort of singleton pregnancies complicated by placental abruption with a live born infant at two academic reference centers in France, from 2006 to 2019. Cases were patients who gave birth to an infant with moderate or severe HIE or death within 28 days (HIE/death group), and controls were patients whose infant did not have any of these outcomes (no-HIE group). Independent risk factors were identified by logistic regression. Binary decision tree discriminant (CART) analysis was performed to define high-risk subgroups of HIE or death. ResultsAmong 152 patients, the infants of 44 (29%) had HIE or death. Out-of-hospital placental abruption and fetal bradycardia at admission were more frequent in cases than in controls: 39 (89%) vs 61 (56%), p < .01 and 24 (59%) vs 19 (18%), p < .01, respectively. In multivariate analysis, out-of-hospital placental abruption (aOR, 7.05; 95% CI, 1.94-25.66) and bradycardia at admission (aOR, 8.60; 95% CI, 2.51-29.42) were independently associated with an increased risk of HIE or death. The combination of out-of-hospital placental abruption and bradycardia was the highest risk situation associated with HIE or death (67%). The decision-to-delivery interval was 15 [12-20] minutes among cases. ConclusionOut-of-hospital placental abruption combined with bradycardia at admission was associated with a major risk of moderate or severe HIE or death. An optimal decision-to-delivery interval does not guarantee the absence of an adverse neonatal outcome.

Healthcare organizational factors associated with delayed therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: the LyTONEPAL cohort.

Initiation of therapeutic hypothermia (TH) within 6h of life is a major concern for treating neonatal hypoxic ischemic encephalopathy (HIE). We aimed to determine clinical and healthcare organizational factors associated with delayed TH in a French population-based cohort of neonates with moderate/severe HIE. Time to reach a rectal temperature of 34°C defines optimal and delayed (within and over 6h, respectively) TH. Clinical and healthcare organizational factors associated with delayed TH were analysed among neonates born in cooling centres (CCs) and non-cooling centres (non-CCs). Among 629 neonates eligible for TH, 574 received treatment (91.3%). TH was delayed in 29.8% neonates and in 20.3% and 36.2% of those born in CCs and non-CCs, respectively. Neonates with moderate HIE were more exposed to delayed TH in both CCs and non-CCs. After adjustment for HIE severity, maternal and neonatal characteristics and circumstances of birth were not associated with increased risk of delayed TH. However, this risk was 2 to 5 times higher in maternities with < 1999 annual births, when the delay between birth and call for transfer (adjusted odds ratio [aOR] 2.47, 95% confidence interval [CI] [1.03 to 5.96]) or between call for transfer and admission (aOR 6.06, 95%CI [2.60 to 14.12]) was > 3h and when an undesirable event occurred during transfer (aOR 2.66, 95%CI [1.11 to 6.37]. Conclusion: Increasing early identification of neonates who could benefit from TH and access to TH in non-CCs before transfer are modifiable factors that could improve care of neonates with HIE. Trial registration: The trial was registered at ClinicalTrials.gov (NCT02676063). What is Known: • International recommendations are to initiate therapeutic hypothermia before 6 h of life in neonates with moderate or severe hypoxic ischemic encephalopathy. What is New: •In this French population-based cohort of infants with hypoxic ischemic encephalopathy, nearly one-third of neonates eligible for treatment did not have access to hypothermia in the therapeutic window of 6 h of life. . • Among infants born in non-cooling centres, healthcare organizational factors involved in delayed care were the small size of maternities (1999 annual births), a time interval of more than 3 h between birth and call for transfer and between call for transfer and admission in neonatology, and the occurrence of an undesirable event during transfer.

South African neonates with mild and moderate hypoxic-ischaemic encephalopathy

Background. Clear risk profiles of neonates with mild and moderate hypoxic-ischaemic encephalopathy (HIE) are lacking.Objective. To describe and compare factors associated with mild and moderate HIE in South African neonates.Methods. A prospective, comparative design was used to describe factors among South African neonates with mild (n=13) and moderate (n=33) HIE in an urban tertiary academic hospital. HIE diagnosis and encephalopathy grading were conducted using the modified Sarnat stages. Thompson scores were recorded. Participants’ clinical records were reviewed to identify factors. Descriptive data were obtained. Chi-square and Fisher’s exact tests were used to compare categorical data, and Mann-Whitney tests were used to compare continuous data between groups.Results. Significant differences were found between groups’ admission (p&lt;0.001) and highest Thompson scores (p&lt;0.001). The mild group’s APGAR scores were significantly higher than those of the moderate group at five (p=0.012) and ten minutes (p=0.022). Duration of resuscitation (p=0.011) and time to spontaneous respiration (p=0.012) also differed significantly between groups. Significantly more moderate than mild participants received therapeutic hypothermia (TH) (p&lt;0.001).Conclusion. Clinical tests and management factors differed significantly between groups. The findings provided the multidisciplinary team with an increased understanding of the heterogeneous HIE population and add to existing evidence for identifying neonates eligible for TH in resource-limited settings.

Placental pathology as a marker of brain injury in infants with hypoxic ischemic encephalopathy

BackgroundHypoxic Ischemic Encephalopathy (HIE) can lead to devastating consequences for the affected infant. Although therapeutic cooling benefits infants with moderate and severe HIE, differentiating mild from moderate-severe HIE may be challenging. The placenta reflects the fetal intrauterine environment and may reveal underlying processes that affect brain injury. AimTo describe placental histopathology using the Amsterdam Placental Workshop Group Criteria in different grades of HIE. Study designRetrospective cohort. SubjectsInfants admitted to a tertiary care neonatal intensive care unit with a diagnosis of HIE between 2011 and 2016. Outcome measureMaternal and neonatal clinical variables and placental histopathology using the Amsterdam Placental Workshop Group Criteria were compared between mild and moderate-severe HIE. Mann-Whitney or t-test or ꭓ2 were performed for bivariate associations as appropriate. To explain the relationship between placental pathology and severity of HIE odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using logistic regression models. ResultsOf the 73 infants in the study, 23 had mild and 50 moderate-sever HIE. There was no difference in maternal and neonatal characteristics except for sentinel events which were higher in the moderate- severe group. On placental histopathology, acute inflammation, including fetal inflammatory reaction (FIR) were significantly higher in the moderate-severe group. After adjusting for confounders, FIR remained significantly associated with moderate-severe HIE, ORs 6.29, 95 % CI 1.5–25. ConclusionOur study demonstrates FIR in the placenta is associated with severity of HIE.

Short-term outcome of perinatal hypoxic-ischaemic encephalopathy at Chiang Mai University Hospital, Thailand: a 15-year retrospective study

ABSTRACT Background The outcome of perinatal hypoxic-ischaemic encephalopathy (HIE) in middle-to-low-income countries varies between regions. Objectives To determine the mortality and morbidity, and factors influencing the deaths of infants with perinatal HIE. Methods A retrospective study was conducted at Chiang Mai University Hospital, Thailand. Perinatal HIE infants of >35 weeks gestation, birthweight ≥2000 g and admitted during 2005-2019 were reviewed. Baseline Characteristics, clinical course and outcome at discharge were compared between the period before and after initiation of therapeutic hypothermia (TH). Risk of death in HIE infants who underwent TH was identified Results A total of 162 HIE infants were included. Compared to the period before TH initiation, the mortality rate was significantly decreased in the TH period. (27% vs. 12.8%, p=0.04) Among 100 HIE infants who underwent TH, the mortality rates was 14%(14/100), of whom 2.5% (2/76) and 50% (12/24) were in the moderate and severe HIE groups. Apgar score at 5 mins ≤1, severe HIE, seizures, hypoglycaemia, organ involvement ≥ five sites, ammonia ≥100 umol/L, lactate ≥14 mmol/L, and requirement for two or more inotropic drugs were risks of death. Multivariate analysis demonstrated that severe HIE (aOR 732.8, 95% CI 4.7–114643, p=0.01) and a need for two or more inotropic drugs (aOR 45.7, 95% CI 1.5–1040, p=0.029) were significant factors for mortality. Conclusion In the period of TH, perinatal HIE infants had decreased mortality. Severe HIE and a need for two or more inotropic drugs were associated with death in the infant with HIE who underwent TH. Abbreviations: AED: anti-epileptic drug; BW, birthweight; CI: confidence interval; CMU: Chiang Mai University; EEG: electro-encephalogram; GA: gestational age; HIE: hypoxic-ischaemic encephalopathy; IQR: interquartile range; NICU: neonatal intensive care unit; SD: standard deviation; TH: therapeutic hypothermia.

Brain injury patterns in hypoxic ischemic encephalopathy of term neonates.

Topographic patterns of brain injury in neonates can help with differentiation and prognostic categorization of hypoxic ischemic encephalopathy (HIE). In this study, we quantitatively and objectively characterized the location of hypoxic ischemic lesions in term neonates with varying severity of HIE. We analyzed term neonates (born ≥37 postmenstrual gestational weeks) with MRI diffusion-weighted imaging (DWI) and diagnoses of HIE. Neonates' HIE was categorized into mild, moderate, and severe. The hypoxic ischemic lesions were segmented on DWI series with attention to T1- and T2-weighted images and then co-registered onto standard brain space to generate summation maps for each severity category. Applying voxel-wise general linear models, we also identified cerebral regions more likely to infarct with increasing severity of HIE, after correction for lesion volume and time-to-scan as covariates. We included 33 neonates: 20 with mild, eight with moderate, and five with severe HIE. Infarct volumes (p=.00052) and Appearance, Pulse, Grimace, Activity, and Respiration scores at 1minute (p=.032) differed between HIE severity categories. Hypoxic ischemic lesions in neonates with mild and moderate HIE were predominant in subcortical and deep white matter along the border zones of arterial supply territories, while severe HIE also involved basal ganglia, hippocampus, and thalamus. In voxel-wise analysis, higher severity of HIE was associated with the presence of lesions in hippocampus, thalamus, and lentiform nucleus. In term neonates, mild/moderate HIE is associated with infarctions of arterial territory watershed zones, whereas severe HIE distinctively involves basal ganglia, thalami, and hippocampi.

Non-invasive continuous cardiac output monitoring in infants with hypoxic ischaemic encephalopathy

ObjectiveTo describe early, continuous, non-invasive measures of cardiac output (CO) and evolution over time in infants with hypoxic-ischaemic encephalopathy (HIE).Study designProspective observational study of 44 infants with HIE (23 mild, 17 moderate, 4 severe) and 17 term controls. Infants with HIE had non-invasive CO monitoring (NICOM) continuously in the neonatal unit. Term controls had NICOM recorded at 6 and 24 h. A mixed-modelling approach was used to assess change in CO over time by group.ResultsInfants with moderate HIE have significantly lower CO than the mild group at all timepoints (10.7 mls/kg/min lower, 95% CI:1.0,20.4, p = 0.03) which increases over time, driven by a gradual increase in stroke volume (SV). CO increased further during rewarming predominantly due to an increase in HR.ConclusionTH has a significant impact on HR but SV appears largely unaffected. NICOM may provide a non-invasive, continuous, low-cost alternative to monitoring CO in infants with HIE however further research is warranted.

ROLE OF SERUM S-100B PROTEIN AND MRI IN PREDICTING THE NEUROLOGICAL OUTCOME AND SEQUELAE IN NEONATES ≥ 36 WEEKS WITH BIRTH ASPHYXIA.

A prompt diagnosis of neonatal hypoxic-ischemic encephalopathy (HIE) remains a clinical challenge. This study aimed at exploring the potential of Serum protein S100B as a biomarker for evaluating neonatal HIE in newborns with moderateto-severe hypoxic-ischemic encephalopathy. Blood samples were collected from neonates with mild, moderate, or severe HIE who were admitted to the Department of Neonatology, Madras Medical College (MMC), Chennai between September 2016 to March 2017. The plasma levels of S100 B protein were measured at different time points. Additionally, Neurodevelopmental outcomes were also studied using MRI in surviving infants (&gt; 2 weeks). Eighty-four neonates enrolled in the study had moderate (n = 37), severe (n = 13) and mild HIE (n= 36). At birth, serum protein S100 B increased with the severity of HIE (P &lt; .001), and remained elevated in neonates with moderate to severe HIE. Serum protein S100 B was greater up to 72 hours in moderate to severe vs mild HIE. The Elevated levels of S100B were associated with increased brain injury as studied by MRI. The study suggests S S100 B may serve as a potential biomarker for neonatal mild HIE (n=36), moderate (n=37) and severe (n=13) could be used for stratication at birth as elevated levels are correlated with the severity of HIE.

Evolution of early cerebral NIRS in hypoxic ischaemic encephalopathy.

AimTo describe early cerebral oxygenation (cSO2) and fractional tissue oxygen extraction (FTOE) values and their evolution over the first days of life in infants with all grades of hypoxic‐ischaemic encephalopathy (HIE) and to determine whether cSO2 and FTOE measured early (6 and 12 h) can predict short‐term outcome.MethodsProspective, observational study of cerebral near‐infrared spectroscopy (NIRS) in infants >36 weeks' gestation with HIE. Ten one‐hour epochs of cSO2 and FTOE were extracted for each infant over the first 84 h. Infants with moderate and severe HIE received therapeutic hypothermia (TH). Abnormal outcome was defined as abnormal magnetic resonance imaging (MRI) and/or death.ResultsFifty‐eight infants were included (28 mild, 24 moderate, 6 severe). Median gestational age was 39.9 weeks (IQR 38.1–40.7) and birthweight was 3.35 kgs (IQR 2.97–3.71). cSO2 increased and FTOE decreased over the first 24 h in all grades of HIE. Compared to the moderate group, infants with mild HIE had significantly higher cSO2 at 6 h (p = 0.003), 9 h (p = 0.009) and 12 h (p = 0.032) and lower FTOE at 6 h (p = 0.016) and 9 h (0.029). cSO2 and FTOE at 6 and 12 h did not predict abnormal outcome.ConclusionInfants with mild HIE have higher cSO2 and lower FTOE than those with moderate or severe HIE in the first 12 h of life. cSO2 increased in all grades of HIE over the first 24 h regardless of TH status.

Factors Associated with the Transition Time to Full Enteral Feeding in Newborns with Hypoxic Ischemic Encephalopathy

Background: We aimed to assess the factors associated with the transition time to full enteral feeding (FEF) in newborns with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Methods: We obtained data retrospectively from medical records of the neonates diagnosed with HIE and treated by therapeutic hypothermia to evaluate the factors associated with transition time to FEF. Results: Sixty-one neonates were included in the study. The median gestational age (GA) and birth weight were 39 (37–40) weeks and 3245 (2715–3575) grams, respectively. APGAR scores at the first and fifth minutes were 3 (1–5) and 6 (4–7), respectively. Fifty-seven (93.4%) of the newborns were diagnosed as having moderate HIE, and 4 (6.6%) of them had severe HIE. Transition time to FEF was found to be negatively correlated with gestational week (r, P: -0.280, 0.029) and birth weight (r, P: -0.315, 0.013); and positively correlated with lactate (r, P: 0.295, 0.044), BUN (r, P: 0.285, 0.026) and creatinine levels (r, P: 0.345, 0.007); duration of invasive (r, P: 0.565, 0.0001) and non-invasive mechanical ventilation (r, P: 0.261, 0.042), use of antibiotics (r, P: 0.556, 0.0001) and inotropic agents (r, P: 0.524, 0.0001) and hospitalization (r, P: 0.654, 0.0001). Conclusion: Clinicians should be more careful while starting to feed babies undergoing therapeutic hypothermia with higher lactate levels and impaired renal functions, and should be encouraged to feed clinically stable neonates with HIE as soon as possible, as the transition time to FEF could be related with better clinical outcomes.

Microstructural Alterations in Projection and Association Fibers in Neonatal Hypoxia-Ischemia.

Diffusion MRI (dMRI) is known to be sensitive to hypoxic-ischemic encephalopathy (HIE). However, existing dMRI studies used simple diffusion tensor metrics and focused only on a few selected cerebral regions, which cannot provide a comprehensive picture of microstructural injury. To systematically characterize the microstructural alterations in mild, moderate, and severe HIE neonates compared to healthy neonates with advanced dMRI using region of interest (ROI), tract, and fixel-based analyses. Prospective. A total of 42 neonates (24 males and 18 females). 3-T, diffusion-weighted echo-planar imaging. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) were calculated in 40 ROIs and 6 tracts. Fixel-based analysis was performed to assess group differences in individual fiber components within a voxel (fixel). One-way analysis of covariance (ANCOVA) to compare dMRI metrics among severe/moderate/mild HIE and control groups and general linear model for fixel-wise group differences (age, sex, and body weight as covariates). Adjusted P value < 0.05 was considered statistically significant. For severe HIE, ROI-based analysis revealed widespread regions, including the deep nuclei and white matter with reduced FA, while in moderate injury, only FC was decreased around the posterior watershed zones. Tract-based analysis demonstrated significantly reduced FA, FD, and FC in the right inferior fronto-occipital fasciculus (IFOF), right inferior longitudinal fasciculus (ILF), and splenium of corpus callosum (SCC) in moderate HIE, and in right IFOF and left anterior thalamic radiation (ATR) in mild HIE. Correspondingly, we found altered fixels in the right middle-posterior IFOF and ILF, and in the central-to-right part of SCC in moderate HIE. For severe HIE, extensive microstructural injury was identified. For moderate-mild HIE, association fiber injury in posterior watershed area with a rightward lateralization was found. 1 TECHNICAL EFFICACY: Stage 3.

Prognostic value of colour Doppler brain sonography for the neurodevelopmental outcome in term neonates with hypoxic ischaemic encephalopathy.

Aim To determine a prognostic value of cerebral blood flow parameters for the development of neurological sequelae in term neonates with hypoxic ischaemic encephalopathy (HIE). Methods We reviewed medical records of 47 term neonates with HIE who survived until the age of 12 months of life. According to the Sarnat and Sarnat clinical score, neonates were divided into 3 groups: mild HIE, moderate HIE and severe HIE. All included neonates had the colour Doppler brain sonography performed in the first 24 hours of life. The neurological assessment was done at the age of 12 months of life by using the Denver Developmental Screening Test (DDST). Logic regression analysis was performed using the colour doppler brain sonography parameters with the development of neurological impairment as the primary outcome. Results Out of 47 neonates, 19 (40.4%) were with mild, 17 (36.2%) with moderate and 11 (23.4%) with severe HIE. The values of cerebral blood flow parameters and resistance index (RI) significantly correlated with the neurological impairment at the age of 12 months of life (p<0.001). The limit value of RI indicating the poor neurodevelopmental outcome was 0.81, sensitivity 80%, specificity 85.3%, positive predictive value 52.2% and negative predictive value 95.2%. Conclusion The cerebral blood flow parameters measured with colour doppler brain sonography are good indicators of the severity of HIE and later neurodevelopmetal outcome.

Selective head cooling or whole body cooling? That is the question

Background. Studies to date support the beneficial effect that therapeutic hypothermia (TH) has on neonates with hypoxic-ischemic encephalopathy. TH can be delivered in two ways: selective head cooling (SHC) or therapeutic whole-body cooling (WBC). The purpose of this review is to examine the literature to expose the advantages and disadvantages of the two methods of performing TH in neonates diagnosed with moderate or severe HIE and to investigate whether one method is superior to the other. Methods. We started from the data from the Cochrane review published in 2013 [1] and we want to bring new information from recent clinical studies comparing the two TH methods (SHC vs WBC). Clinical studies were searched and analyzed by a single individual (through dedicated search engines such as Google Scholar, PubMed, and Scopus). We have included clinical studies from the last 7 years comparing the two ways of performing TH (SHC vs. WBC). We selected only the articles that compared the two methods and excluded the articles describing only one method. Results. After excluding the clinical trials that did not meet the eligibility criteria, 5 clinical trials remained (n = 256 neonates). Analysis of these studies supports the idea that both modalities of therapeutic hypothermia cool central nervous system (CNS) structures and have a similar neurodevelopmental prognosis among surviving neonates. Also, there are no significant differences in terms of short-term neurological prognosis, as well as the adverse effects that may occur in neonates with moderate or severe HIE (hypoxic-ischemic encephalopathy) treated with SHC or WBC; although some studies note the presence of more severe, statistically significant lesions among patients treated with SHC compared to those treated with WBC. Conclusions. Prospective, randomized studies on a much larger scale are needed to track the adverse effects that the two HT methods may have on patients, as well as long-term neurological and cognitive prognosis. Until now, there is no clear evidence that one of these two methods is definitely safer or more reliable than the other.

Adherence to hypothermia guidelines in newborns with hypoxic-ischemic encephalopathy

IntroductionWe do not have population data in Spain on the application of therapeutic hypothermia (TH). The objective was to examine adherence to management standards during TH of infants with hypoxic-ischemic encephalopathy (HIE). MethodMulticenter observational cohort study from the beginning of TH (year 2010) in 5 hospitals in a Spanish region, until year 2019. Results133 patients were recruited, 72% diagnosed with moderate HIE and the rest of them with severe HIE. In 84% of infants, passive hypothermia was started at birth. Active TH was started at a median age of 5 h of life (IQR 3.3; 6.3), although the central targeted temperature (33−34 °C) was reached at a median age of 3.5 h (IQR 1; 6). Those born extramural, initiated active TH 3.3 h on average later than those born intramural, but without differences in the age at which the targeted temperature was reached.Sedoanalgesia was used in 97%. 100% were monitored with amplitude-integrated EEG and 59% with cerebral oxymetry. MRI was performed in 94% with moderate HIE vs. 65% with severe; P < .001. Neuron-specific enolase in cerebrospinal fluid was determined in 42%. The average duration of rewarming was median 10 h (IQR 8; 12), with no differences depending on the degree of HIE (P = .57). ConclusionsThe implementation of TH successfully met the standards. However, aspects of care that could be improved were detected. Auditing newborn care with HIE is crucial to achieving programs with a high quality of care in each region

Defining Longer-Term Outcomes in an Ovine Model of Moderate Perinatal Hypoxia-Ischemia

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 1 million infants born with HIE each year survive with cerebral palsy and/or serious cognitive disabilities. While infants born with mild and severe HIE frequently result in predictable outcomes, infants born with moderate HIE exhibit variable outcomes that are highly unpredictable. Here, we describe an umbilical cord occlusion (UCO) model of moderate HIE with a 6-day follow-up. Near-term lambs (n = 27) were resuscitated after the induction of 5 min of asystole. Following recovery, lambs were assessed to define neurodevelopmental outcomes. At the end of this period, lambs were euthanized, and brains were harvested for histological analysis. Compared with prior models that typically follow lambs for 3 days, the observation of neurobehavioral outcomes for 6 days enabled identification of animals that recover significant neurological function. Approximately 35% of lambs exhibited severe motor deficits throughout the entirety of the 6-day course and, in the most severely affected lambs, developed spastic diparesis similar to that observed in infants who survive severe neonatal HIE (severe, UCOs). Importantly, and similar to outcomes in human neonates, while initially developing significant acidosis and encephalopathy, the remainder of the lambs in this model recovered normal motor activity and exhibited normal neurodevelopmental outcomes by 6 days of life (improved, UCOi). The UCOs group exhibited gliosis and inflammation in both white and gray matters, oligodendrocyte loss, neuronal loss, and cellular death in the hippocampus and cingulate cortex. While the UCOi group exhibited more cellular death and gliosis in the parasagittal cortex, they demonstrated more preserved white matter markers, along with reduced markers of inflammation and lower cellular death and neuronal loss in Ca3 of the hippocampus compared with UCOs lambs. Our large animal model of moderate HIE with prolonged follow-up will help further define pathophysiologic drivers of brain injury while enabling identification of predictive biomarkers that correlate with disease outcomes and ultimately help support development of therapeutic approaches to this challenging clinical scenario.

Risk factors for hypoxic-ischemic encephalopathy or neonatal death in placental abruption

To identify risk factors associated with moderate or severe hypoxic-ischemic encephalopathy (HIE) or neonatal death among women with a symptomatic placental abruption. A retrospective, comparative, bicentric study at two academic tertiary centers in Île-de-France, from 2006 to 2019. Singleton pregnancies complicated by confirmed placental abruption at delivery with a live birth infant were eligible. Primary outcome was the occurrence of moderate or severe HIE or neonatal death. Among 152 women, 44 (29%) women delivered an infant with a moderate or severe HIE or a neonatal death, (HIE/death group) and were compared to 108 women who delivered infants without these outcomes (non-HIE group). One hundred (66%) placental abruptions occurred out of-hospital, and were more frequent in the HIE/death group than in the non-HIE group [39 (89%) vs. 61 (56%), P < 0.01]. Fetal bradycardia was more frequent in the HIE/death group [24 (55%) vs. 19 (18%), P < 0.01]. The decision-to-delivery interval was shorter in the HIE/death group (15 [12–20] vs. 20 [15–30] minutes, P < 0.01). In multivariate analysis, urgent delivery for an out-of-hospital placental abruption (aOR 5.79 [2.07–16.17]) and fetal bradycardia (aOR: 8.55 [3.13–23.32]) were independently associated with an increased risk of moderate or severe HIE or neonatal death. The presence of a bradycardia was the most discriminating factor associated with moderate or severe HIE or death (59%). The highest risk situations were bradycardia and urgent cesarean delivery for an out-of-hospital placental abruption (68%). Out-of-hospital placental abruption is associated with a major risk of moderate or severe HIE or death in the presence of a fetal bradycardia. An optimal decision-to-delivery interval that is difficult to improve does not guarantee the absence of severe neonatal complications.