History Of Hypoxic-ischemic Encephalopathy Research Articles

A Systematic Review of the Relationship Between Neonatal Hypoxic-Ischemic Encephalopathy and Long-Term Cognitive Outcomes: Where Do We Stand?

This study aims to systematically review the existing literature on long-term cognitive outcomes in neonates with hypoxic-ischemic encephalopathy (HIE). A thorough search of PubMed, MEDLINE, and Embase was conducted to find studies that satisfied the inclusion requirements. Rayyan (Qatar Computing Research Institute, Doha, Qatar) was utilized during the whole operation.Our results included seven studies with a total of 521 patients and 247 (47.4%) were females. All of the included participants were assessed for the incidence of cognitive functions following hypothermia therapy. Newborns with significant HIE are at high risk for neurodevelopmental complications even in the absence of magnetic resonance imagining (MRI) abnormalities, such as poor performance score and hearing-language score, functional status, delayed language skills, emotional processing, sensory movement, learning, and memory.Independent of motor deficits, participants with a history of HIE are susceptible to issues with cognition and executive function during late childhood and adolescence. It is crucial to keep an eye on their intellectual development after infancy since cognitive dysfunction and memory problems might manifest subtly or not at all in the early years of life, but they can cause problems in later childhood and adolescence. Long-term follow-up research is also required to ascertain whether the enhanced cognitive outcomes will continue throughout adolescence. Even in cases where overt neuromotor abnormalities are not evident, children with watershed injuries on brain MRIs should be closely monitored to evaluate cognitive function, particularly language development.

Reduced Hippocampal Volumes in Children with History of Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia.

Hypoxic ischemic encephalopathy (HIE) remains a significant cause of disability despite treatment with therapeutic hypothermia (TH). Many survive with more subtle deficits that affect daily functioning and school performance. We have previously shown an early indication of hippocampal changes in infants with HIE despite TH. The aim of this study was to evaluate the hippocampal volume via MRI and memory function at 5 years of age. A cohort of children followed from birth returned for a 5-year follow-up (n = 10 HIE treated with TH, n = 8 healthy controls). The children underwent brain MRI and neurodevelopmental testing to assess their brain volume, general development, and memory function. Children with HIE had smaller hippocampal volumes than the controls despite no differences in the total brain volume (p = 0.02). Children with HIE generally scored within the average range on developmental testing. Though there was no difference in the memory scores between these groups, there was a positive within-group correlation between the hippocampal volume and memory scores in children with HIE (sentence recall r = 0.66, p = 0.038). There was no relationship between newborn memory function and 5-year hippocampal size. Children with HIE treated with TH experienced significant and lasting changes to the hippocampus despite improvements in survival and severe disability. Future studies should target diminishing injury to the hippocampus to improve overall outcomes.

Expanding Understanding of Electrocochleography in Cochlear Implantation: Auditory Neuropathy Spectrum Disorder With Normal Pure Tone Average.

Describe the preoperative decision-making, intraoperative electrocochleographic (ECoG) findings, and outcome of cochlear implantation (CI) in a patient with auditory neuropathy spectrum disorder (ANSD) and normal pure-tone thresholds. A 19-year-old with a history of hypoxic ischemic encephalopathy and seizures was referred for hearing rehabilitation in the setting of typical hearing by pure tone audiometry but poor speech understanding. A diagnosis of ANSD was made based on acoustic brainstem response (ABR), distortion product otoacoustic emission, and acoustic reflex testing. Imaging revealed no central cause of hearing impairment. Right-sided CI. Preoperative and postoperative audiometric data. Intraoperative ECoG. Preoperatively the patient underwent comprehensive audiologic testing with behavioral audiometry, ABR testing, and CI candidacy evaluation. In the right ear, the pure tone average (PTA) was 15 dB and word recognition score was 36%. ABR confirmed ANSD. Preoperative CNC and AzBio in quiet were 8% and 0%, respectively. Intraoperative ECoG amplitudes and audiometry showed responses in the 100 uV range and estimated PTA of 42 dB HL. Postoperative testing at 1-month post-initial activation revealed PTA of 45 dB HL and unchanged word and sentence scores. However, the patient cites an improved ability to communicate and increased confidence and averages over 14 hours of device use daily. To our knowledge, this is the first reported case of CI in an ear with normal PTA. Given that nearly all presently available ECoG data comes from patients with greater degrees of hearing loss, this unique case adds to our understanding of hearing preservation in CI.

Frequency of various causes of acute kidney injury in neonates in a tertiary care hospital neonatal intensive care.

Objective: To determine the frequency of causes of acute kidney injury in neonatal. Study Design: Cross Sectional study. Setting: Neonatology Ward, Saidu Teaching Hospital. Period: July 2020 to June 2021. Material & Methods: A total of 257 neonates were selected having AKI and included in the study. Various causes and risk factors for AKI were assessed and patients were followed till the outcome. Results: A total of 257 patients having AKI were included and data was collected. Of the total selected newborns gender distribution was 57.97% (149/257) males and female were 42.02% (108/257). Mean age was 5.1 ± 4.6 days. 73.15% babies were delivered at term gestation and 26.84% were delivered preterm. 90.27 % babies were delivered through normal vaginal delivery and 9.7% were delivered through caesarean section. Among the total 257 included babies 27.62% were having history of hypoxic ischemic encephalopathy and 45.52% were diagnosed as sepsis on positive blood culture or septic screening. Oliguria was present in only 38.13% of the babies and urine output was normal in 61.86%. 95.71% babies were not having renal malformations. Renal profile of the babies showed with mean serum creatinine of 2.57 mg/dl. Mean sodium level was 139.16 mg/dl and mean potassium level was 3.59 mg/dl. 26.45% of the total patients died and the mortality rate was 29% in patient having sepsis as compared to 25% of patient having hypoxic ischemic encephalopathy. Conclusion: AKI in NICU is very common and needs a proper evaluation and management strategies. Neonatologist should be aware of the various causes of AKI and should be able to diagnose it on time. In neonates having AKI, oliguria is not that much common therefore it is recommended not to wait for a decrease urine output but to screen all the high risk neonates for AKI with serum creatinine level. Mortality in neonates due to AKI was high specifically in male gender having sepsis, HIE or oliguria.

Postneonatal Epilepsy and Psychomotor Developmental Retardation Risk Factors in Term Neonatal Convulsions Without Hypoxic Ischemic Encephalopathy

Objective: Neonatal convulsions may be an early sign of brain injury and the presence of convulsions in the neonatal period has been associated with long-term sequelaes such as mental retardation, postnatal epilepsy and death. We aimed to determine associations of etiological factors with neurodevelopment and postneonatal epilepsy and evaluate the risk factors in newborns with neonatal convulsions that were not related to hypoxic-ischemic encephalopathy. Material and Methods: This study included full-term infants who were born between January 2010 and December 2014 and had neonatal convulsion history, had no history of hypoxic-ischemic encephalopathy and were followed for at least 1 year at our neurology clinic. Results: Forty-nine patients were included to the study. Among the identified etiologies on first clinical visit, hypoglycemia was the most common cause which was presented in 11 (40.74%; 11/27 patients) patients. During follow-up, 22.4% (n=11) of patients developed postneonatal epilepsy. In 4 of 7 patients with abnormal Bayley II test results, epilepsy developed in the follow-up. The risk for development of postneonatal epilepsy was significantly associated with abnormal neurological findings, such as cerebral palsy or significant delays in developmental stages; being not benefited from acute treatment and follow-up abnormal EEG findings of the patients. Conclusion: Hypoglycemia should be primarily investigated and treated in term neonatal seizures without hypoxia. Abnormal neurological findings, being not benefited from the acute treatment and follow-up EEG findings were associated with developing epilepsy. In the literature, most of the studies were limited due to short follow-up periods. More information about prognostic factors in neonatal convulsions and the occurrence of postneonatal epilepsy is needed.

Reduced Hippocampal Volumes in Children with History of Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia

Reduced Hippocampal Volumes in Children with History of Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia

Evaluation of the seizure control and the tolerability of ketogenic diet in Chinese children with structural drug-resistant epilepsy

ObjectivesIn this study, we aimed to evaluate the efficacy and tolerability of ketogenic diet (KD) in Chinese children with drug-resistant epilepsy (DRE) due to structural etiology. MethodsWe retrospectively analyzed data from 23 pediatric patients with DRE due to structural etiology who were treated with KD at Department of Neurology, between May 2014 and December 2020. Based on etiological classifications, the patients were divided into a neonatal brain injury (Group 1), an intracranial infection group (Group2) and a group that showed malformations of cortical development (MCDs) (Group 3). ResultsThe 23 patients remained on the KD for a mean duration of 15.3 ± 9.7 months. The response rates for the control of seizures were 60.9% (14/23), 52.2 % (12/23), 47.8% (11/23) at 3, 6 and 12 months, respectively. Subjective improvements in cognition were observed in 87.0% (20/23) of the children during follow-up. Reductions in the frequency of seizures of > 50% were more commonly achieved by patients in group 1 (75.0%, 9/12) compared to the patients in groups 2 (60.0%, 3/5) and 3 (33.4%, 2/6). Further analysis of the patients in Group 1 showed that children with a history of hypoxic ischemic encephalopathy (HIE) (100.0%, 6/6) had the highest rate of > 50% seizure reduction. The main reasons for the discontinuation of the KD were due to lack of efficacy and poor compliance. Most of the side effects associated with the KD diet were minor and easily corrected by appropriately adjusting the diet. Only 1 patient discontinued the diet due to severe refusal to eat. ConclusionsKD is an effective and safe treatment for Chinese children with DRE due to structural etiology. Better efficacy of seizure control was observed in patients with a history of neonatal brain injury. Patients with DRE secondary to HIE may be particularly responsive to the KD therapy, and so KD should be considered earlier in those patients.

Long-Term Outcomes after Neonatal Hypoxic-Ischemic Encephalopathy in the Era of Therapeutic Hypothermia: A Longitudinal, Prospective, Multicenter Case-Control Study in Children without Overt Brain Damage.

Background. Data on long-term outcomes in the era before therapeutic hypothermia (TH) showed a higher incidence of cognitive problems. Since the introduction of TH, data on its results are limited. Methods. Our sample population consisted of 40 children with a history of hypoxic-ischemic encephalopathy (HIE) treated with TH, with an average age of 6.25 years (range 5.5, 7.33), 24 (60%) males; and 33 peers with an average age of 8.8 years (6.08, 9.41), 17 (51%) males. Long-term follow-up data belong to two centers in Padova and Torino. We measured general intelligence (WPPSI-III or WISC-IV) and neuropsychological functioning (language, attention, memory, executive functions, social skills, visual motor abilities). We also administered questionnaires to their parents on the children’s psychopathological profiles and parental stress. Results. We found differences between groups in several cognitive and neuropsychological domains: intelligence, visuomotor skills, executive functions, and attention. Interestingly, IQ test results effectively differentiated between the groups (HIE vs. controls). Furthermore, the incidence of psychopathology appears to be significantly higher in children with HIE (35%) than in control peers (12%). Conclusions. Our study supports previous findings on a higher incidence of neuropsychological, cognitive, and psychopathological sequelae after HIE treated with TH. As hypothesized, TH does not appear to ameliorate the outcome after neonatal HIE in those children who survive without major sequelae.

Cognitive outcomes in late childhood and adolescence of neonatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy with a global incidence of approximately 1 to 8 per 1,000 live births. Neonatal encephalopathy can cause neurodevelopmental and cognitive impairments in survivors of hypoxic-ischemic insults with and without functional motor deficits. Normal neurodevelopmental outcomes in early childhood do not preclude cognitive and behavioral difficulties in late childhood and adolescence because cognitive functions are not yet fully developed at this early age. Therapeutic hypothermia has been shown to significantly reduced death and severe disabilities in term newborns with HIE. However, children treated with hypothermia therapy remain at risk for cognitive impairments and follow-up is necessary throughout late childhood and adolescence. Novel adjunctive neuroprotective therapies combined with therapeutic hypothermia may enhance the survival and neurodevelopmental outcomes of infants with HIE. The extent and severity of brain injury on magnetic resonance imaging might predict neurodevelopmental outcomes and lead to targeted interven tions in children with a history of neonatal encephalopathy. We provide a summary of the long-term cognitive outcomes in late childhood and adolescence in children with a history of HIE and the association between pattern of brain injury and neurodevelopmental outcomes.

Identifying Risk Factors That Distinguish Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection From Common Upper Respiratory Infections in Children.

BackgroundDemographic and clinical risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children presenting with respiratory viral symptoms are not well defined. An understanding of risk factors for SARS-CoV-2 infection can help prioritize testing.MethodologyWe evaluated potential demographic and clinical factors in children who had respiratory viral symptoms and were tested by polymerase chain reaction (PCR) for SARS-CoV-2 and other respiratory viral infections.ResultsAmong the 263 symptomatic children tested for routine seasonal respiratory viruses by PCR, 18 (6.8%) tested positive for SARS-CoV-2. Overall, 22.2% of SARS-CoV-2-infected children and 37.1% of SARS-CoV-2-uninfected children had infection with one or more non-SARS-CoV-2 pathogens (p = 0.31). Higher proportions of children with compared to without SARS-CoV-2 infection were male (77.8 vs. 51.8%, p = 0.05), Hispanic (44.4% vs. 9.8%, p < 0.001), or had the symptoms of fatigue (22.2% vs. 2.5%, p = 0.003) or anosmia/ageusia (11.1% vs. 0%, p = 0.004). History of hypoxic-ischemic encephalopathy (HIE) and obesity were more common in children with versus without SARS-CoV-2 infection (11.1% vs. 1.2%, p = 0.04, and 11.1% vs. 0%, p = 0.004, respectively). In a multivariate analysis, Hispanic ethnicity, symptoms of fatigue or anosmia/ageusia, and presence of obesity (as noted on physical examination) or HIE were independently associated with SARS-CoV-2 infection. Numbers in each category were small, and these preliminary associations require confirmation in future studies.ConclusionsIn this area of the United States, infection with other viruses did not rule out infection with SARS-CoV-2. Additionally, children with respiratory viral symptoms who were of Hispanic ethnicity, had symptoms of weakness/fatigue, or had obesity or HIE were at an increased risk for SARS-CoV-2 infection. Future studies should assess if these factors are associated with risk in populations in other areas of the United States.

Study of the modulatory mechanism of the miR-182-Clock axis in circadian rhythm disturbance after hypoxic–ischemic brain damage

Hypoxic–ischemic encephalopathy (HIE) in neonates can lead to severe chronic neurological deficit, including mental retardation, epilepsy, and sleep–wake cycle (SWC) disorder. Among these defects, little is known about the molecular mechanism of circadian rhythm disorder after HIE. Therefore, further study of sleep problems and its mechanism in HIE children will provide new ideas for clinical treatment of HIE children. For pediatric patients with cerebral ischemia, somnipathy often occurs due to visual and airway abnormalities. From May 2010 to August 2013, 128 newborns with history of HIE were followed up. Meanwhile, 88 normal full-term newborns in the same period were taken as the control group. The clinical data of the patients were collected and the sleep status was assessed by questionnaire. To establish the hypoxic–ischemic brain injury model of neonatal rats and analyze the mechanism of mir-182 in the circadian rhythm disorder caused by pineal function injury. The core clock genes during the regulation of the circadian clock were explored by bioinformatics methods. Patients’ sleep quality was affected by the circadian rhythm and respiratory problems; the pineal gland can regulate the core clock genes in the circadian clock during regulation. miR-182 was highly expressed in the pineal gland after hypoxic–ischemic brain damage (HIBD). Children with mild and moderate HIE showed significant sleep disorders in varying degrees, which provided a clinical basis for improving the long-term prognosis of children with HIE through targeted treatment of sleep disorders. MiR-182 is highly expressed in the pineal gland and is related to the expression of CLOCK protein. CLOCK gene is the target gene of miR-182, which provides a new target for the treatment of rhythm disorder related to the damage of pineal function caused by HIBD.

MR Imaging of hypoxic ischemic encephalopathy – Distribution Patterns and ADC value correlations

Background and purposeNeonatal hypoxic-ischemic encephalopathy causes hypoxic brain injury. Due to differences in brain maturity at time of insult, severity of hypotension and duration of insult, there are four distinct patterns of brain injury. Magnetic resonance imaging is the most sensitive modality for evaluating these patterns of brain injury. Additional role of Diffusion weighted imaging and ADC values can be useful in the evaluation of such cases. We conducted this study to analyse the usefulness of ADC values in the brain tissue affected by hypoxic-ischemic injury. Materials and MethodsWe conducted a prospective study of all the patients referred to our department for magnetic resonance scanning of brain with history of hypoxic ischemic encephalopathy and clinical features cerebral palsy. 23 Cases with imaging manifestations of hypoxic ischemic encephalopathy were included in the study. We studied distribution patterns of HIE in our cases and calculated the ADC values of involved as well as normal grey and white matter. Further, sensitivity, specificity, predictive values, and likelihood ratios for each dichotomized diffusion and ADC values were obtained Wilson Score method. ResultsThe most common distribution pattern in our study was involvement of peri-rolandic area (15 cases, 65%). ADC values were significantly (p < 0.005) increased in abnormal white matter. No significant changes (p = 0.8) were seen in ADC values of normal and abnormal grey matter. ConclusionsDue to significant increase in ADC values of affected white matter, ADC value can be used as a marker to detect chronic sequel of hypoxic ischaemic brain injury. Another observation was the perirolandic brain tissue being most common area of involvement in the cases with cerebral palsy.

Electroencephalogram abnormalities in full term infants with history of severe asphyxia

ingtool used to determine developmental and electrical problemsin the brain. A history of severe asphyxia is a risk factor for thesebrain problems in infants.Objective To evaluate the prevalence of abnormal EEGs infull term neonates and to assess for an association with severeasphyxia, hypoxic ischemic encephalopathy (HIE), and spontaneousdelivery.Methods This cross-sectional study was conducted at thePediatric Outpatient Department of Sanglah Hospital, Denpasar,from November 2013 to January 2014. Subjects were fullterminfants aged 1 month who were delivered and/or hospitalized atSanglah Hospital. All subjects underwent EEG. The EEGs wereinterpreted by a pediatric neurology consultant, twice, with aweek interval between readings. Clinical data were obtainedfrom medical records. Association between abnormal ECG andsevere asphyxia were analyzed by Chi-square and multivariablelogistic analyses.Results Of 55 subjects, 27 had a history of severe asphyxia and 28were vigorous babies. Forty percent (22/55) of subjects had abnormalEEG findings, 19/22 of these subjects having history of severeasphyxia, 15/22 had history of hypoxic-ischemic encephalopathy(HIE), and 20/22 were delievered vaginally. There were strongcorrelations between the prevalence of abnormal EEG and historyof severe asphyxia, HIE, and spontaneous delivery.Conclusion Prevalence of abnormal EEG among full-term neonatesreferred to neurology/growth development clinic is around40%, with most of them having a history of severe asphyxia. AbnormalEEG is significantly associated to severe asphyxia, HIE, andspontaneous delivery.

When health care professionals say "more" and parents say "enough".

The aim of the present article is to provide an overview of the myriad bioethical issues faced when a family believes that interventions are not in the child’s best interest, but the clinician believes otherwise. The present article will illustrate how an analysis of the ethical issues can provide a way forward. CASE PRESENTATION JD is a two-year-old boy with a history of hypoxic ischemic encephalopathy who subsequently developed severe cerebral palsy. Although he is wheelchair-bound, his family believes that his quality of life is good. He is able to communicate through sounds and gestures, enjoys movies and books – especially cartoons – and loves to interact with their dog. However, over the course of the past year, JD has not been growing well and has experienced significant reflux despite maximizing anti-reflux medications. He has experienced two episodes of aspiration pneumonia, which were managed with oral antibiotics, and has fallen off his growth curve for weight despite optimization of his diet. He continues to be exclusively orally fed. JD’s physician has repeatedly recommended a gastrostomy tube (G-tube), which may help with many of JD’s issues (ie, weight gain, aspiration pneumonia); however, his parents have consistently declined this option. Both the physician and JD’s parents are becoming increasingly frustrated with this topic of conversation because they do not fully appreciate one another’s point of view. A common pitfall in situations such as this can occur when one party assumes that they know the other’s intentions (1). Misperceptions about motivation and goals can be easily resolved through open communication. Therefore, in the present analysis, we will explore the perspectives of the parents and clinician and their intentions.