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Anales de Pediatria Oct 2022Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure...
Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure (MOF). This ailment may result from the redistribution of blood flow, which would preserve the perfusion of vital organs such as the heart, brain and adrenal glands at the expense of other organs. The objective of the study was to determine the incidence and aetiopathogenesis of failure in the organs most frequently involved in neonatal MOF following perinatal asphyxia. We conducted a systematic literature search in the PubMed, Scopus and Cochrane Library databases using the MeSH terms (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) and (liver/kidney/digestive OR gastrointestinal/heart injury AND ischemia AND hypoxia AND neonat*). We selected clinical and preclinical studies published after 2000 and excluded case series, letters to the editor, cohort studies without comparison groups and abstracts. In this study, we found that MOF associated with perinatal asphyxia is a frequent phenomenon with a relevant impact on neonatal morbidity and mortality, as it can cause changes not only in the kidney, liver and gastrointestinal tract, but also cardiomyopathy if the ailment is protracted or severe.
Topics: Asphyxia; Asphyxia Neonatorum; Brain; Female; Humans; Hypoxia; Infant, Newborn; Multiple Organ Failure; Pregnancy
PubMed: 36115781
DOI: 10.1016/j.anpede.2022.08.010 -
Advances in Clinical and Experimental... Aug 2020Despite the progress in perinatal care, perinatal asphyxia (PA) remains a significant problem in neonatology. The development of therapeutic hypothermia (TH) has... (Review)
Review
Despite the progress in perinatal care, perinatal asphyxia (PA) remains a significant problem in neonatology. The development of therapeutic hypothermia (TH) has improved the prognosis, but it still remains uncertain in hypoxic neonates. The evaluation of the severity of ischemia/hypoxia after birth is crucial to the choice of treatment, and with accurate long-term prognosis, appropriate further patient care can be planned. This article presents various methods for the preliminary assessment of brain damage and prognosis in newborns with PA treated with TH. The importance of assessing the neurological condition and the usefulness of laboratory and electrophysiological testing and imaging are discussed. New methods are also noted, which are at the stage of clinical trials. A combination of the prognostic tests presented in this article can provide greater prognostic accuracy for predicting long-term neurological outcomes in infants with hypoxic-ischemic encephalopathy (HIE) undergoing TH than either of these tests independently. Acknowledging the limitations of individual tools in certain clinical situations and the integration of the information available from multiple biomarkers may help improve the accuracy of prognostication.
Topics: Asphyxia; Asphyxia Neonatorum; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant; Infant, Newborn; Prognosis
PubMed: 32820870
DOI: 10.17219/acem/124437 -
World Journal of Pediatrics : WJP Jun 2023Current diagnostic criteria for hypoxic-ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify... (Review)
Review
BACKGROUND
Current diagnostic criteria for hypoxic-ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610).
DATA SOURCES
Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English original papers analyzing samples from newborns > 36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included. Bias was assessed by the Newcastle-Ottawa Scale. The search and data extraction were verified by two authors separately.
RESULTS
From 373 papers, 30 met the inclusion criteria. Data from samples collected in the first 72 hours were extracted, and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia. In addition, the levels of glial fibrillary acidic protein, ubiquitin carboxyl terminal hydrolase isozyme-L1, glutamic pyruvic transaminase-2, lactate, and glucose were elevated in newborns diagnosed with hypoxic-ischemic encephalopathy. Moreover, pathway analysis revealed insulin-like growth factor signaling and alanine, aspartate and glutamate metabolism to be involved in the early molecular response to insult.
CONCLUSIONS
Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers, since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy newborns. However, more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Hypoxia-Ischemia, Brain; Biomarkers; Prognosis; Asphyxia Neonatorum; S100 Proteins; Phosphopyruvate Hydratase
PubMed: 37084165
DOI: 10.1007/s12519-023-00698-7 -
Journal of Global Health 2022Therapeutic hypothermia (TH) is regarded as the most efficacious therapy for neonatal hypoxic encephalopathy. However, limitations in previous systematic reviews and the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Therapeutic hypothermia (TH) is regarded as the most efficacious therapy for neonatal hypoxic encephalopathy. However, limitations in previous systematic reviews and the publication of new data necessitate updating the evidence. We conducted this up-to-date systematic review to evaluate the effects of TH in neonatal encephalopathy on clinical outcomes.
METHODS
In this systematic review and meta-analysis, we searched Medline, Cochrane Library, Embase, LIVIVO, Web of Science, Scopus, CINAHL, major trial registries, and grey literature (from inception to October 31, 2021), for randomized controlled trials (RCT) comparing TH vs normothermia in neonatal encephalopathy. We included RCTs enrolling neonates (gestation ≥35 weeks) with perinatal asphyxia and encephalopathy, who received either TH (temperature ≤34°C) initiated within 6 hours of birth for ≥48 hours, vs no cooling. We excluded non-RCTs, those with delayed cooling, or cooling to >34°C. Two authors independently appraised risk-of-bias and extracted data on mortality and neurologic disability at four time points: neonatal (from randomization to discharge/death), infancy (18-24 months), childhood (5-10 years), and long-term (>10 years). Other outcomes included seizures, EEG abnormalities, and MRI findings. Summary data from published RCTs were pooled through fixed-effect meta-analysis.
RESULTS
We identified 36 863 citations and included 39 publications representing 29 RCTs with 2926 participants. Thirteen studies each had low, moderate, and high risk-of-bias. The pooled risk ratios (95% confidence interval, CI) were as follows: neonatal mortality: 0.87 (95% CI = 0.75, 1.00), n = 2434, = 38%; mortality at 18-24 months: 0.88 (95% CI = 0.78, 1.01), n = 2042, = 51%; mortality at 5-10 years: 0.81 (95% CI = 0.62, 1.04), n = 515, = 59%; disability at 18-24 months: 0.62 (95% CI = 0.52, 0.75), n = 1440, = 26%; disability at 5-10 years: 0.68 (95% CI = 0.52, 0.90), n = 442, = 3%; mortality or disability at 18-24 months: 0.78 (95% CI = 0.72, 0.86), n = 1914, = 54%; cerebral palsy at 18-24 months: 0.63 (95% CI = 0.50, 0.78), n = 1136, = 39%; and childhood cerebral palsy: 0.63 (95% CI = 0.46, 0.85), n = 449, = 0%. Some outcomes showed significant differences by study-setting; the risk ratio (95% CI) for mortality at 18-24 months was 0.79 (95% CI = 0.66,0.93), n = 1212, = 7% in high-income countries, 0.67 (95% CI = 0.41, 1.09), n = 276, = 0% in upper-middle-income countries, and 1.18 (95% CI = 0.94, 1.47), n = 554, = 75% in lower-middle-income countries. The corresponding pooled risk ratios for 'mortality or disability at 18-24 months' were 0.77 (95% CI = 0.69, 0.86), n = 1089, = 0%; 0.56 (95% CI = 0.41, 0.78), n = 276, = 30%; and 0.92 (95% CI = 0.77, 1.09), n = 549, = 86% respectively. Trials with low risk of bias showed risk ratio of 0.97 (95% CI = 0.80, 1.16, n = 1475, = 62%) for neonatal mortality, whereas trials with higher risk of bias showed 0.71 (95% CI = 0.55, 0.91), n = 959, = 0%. Likewise, risk ratio for mortality at 18-24 months was 0.96 (95% CI = 0.83, 1.13), n = 1336, = 58% among low risk-of-bias trials, but 0.72 (95% CI = 0.56, 0.92), n = 706, = 0%, among higher risk of bias trials.
CONCLUSIONS
Therapeutic hypothermia for neonatal encephalopathy reduces neurologic disability and cerebral palsy, but its effect on neonatal, infantile and childhood mortality is uncertain. The setting where it is implemented affects the outcomes. Low(er) quality trials overestimated the potential benefit of TH.
Topics: Asphyxia Neonatorum; Brain Diseases; Cerebral Palsy; Child; Female; Humans; Hypothermia, Induced; Hypoxia; Hypoxia, Brain; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 35444799
DOI: 10.7189/jogh.12.04030 -
Acta Medica Portuguesa May 2024
Topics: Humans; Resuscitation; Infant, Newborn
PubMed: 38744233
DOI: 10.20344/amp.21415 -
Ugeskrift For Laeger Mar 2020Hypoxic-ischaemic encephalopathy is a common cause of death and disability in newborns. Brain damage related to a perinatal insult is the result of a dynamic process,... (Review)
Review
Hypoxic-ischaemic encephalopathy is a common cause of death and disability in newborns. Brain damage related to a perinatal insult is the result of a dynamic process, and its progressing development over time allows for specific interventions to reduce total damage, as described in this review. Despite therapeutic hypothermia which currently is the only treatment available, a considerable number of newborns still have adverse outcomes. Prognosis is evaluated by clinical examination and paraclinical investigations. There is still a need for novel treatments and better prognostic and diagnostic tools to improve outcome.
Topics: Asphyxia; Asphyxia Neonatorum; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Prognosis
PubMed: 32285787
DOI: No ID Found -
BMC Pregnancy and Childbirth Mar 2020The objective of our study was to evaluate the association between perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) with the presence of ante and intrapartum... (Observational Study)
Observational Study
BACKGROUND
The objective of our study was to evaluate the association between perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) with the presence of ante and intrapartum risk factors and/or abnormal fetal heart rate (FHR) findings, in order to improve maternal and neonatal management.
METHODS
We did a prospective observational cohort study from a network of four hospitals (one Hub center with neonatal intensive care unit and three level I Spoke centers) between 2014 and 2016. Neonates of gestational age ≥ 35 weeks, birthweight ≥1800 g, without lethal malformations were included if diagnosed with perinatal asphyxia, defined as pH ≤7.0 or Base Excess (BE) ≤ - 12 mMol/L in Umbical Artery (UA) or within 1 h, 10 min Apgar < 5, or need for resuscitation > 10 min. FHR monitoring was classified in three categories according to the American College of Obstetricians and Gynecologists (ACOG). Pregnancies were divided into four classes: 1) low risk; 2) antepartum risk; 3) intrapartum risk; 4) and both ante and intrapartum risk. In the first six hours of life asphyxiated neonates were evaluated using the Thomson score (TS): if TS ≥ 5 neonates were transferred to Hub for further assessment; if TS ≥ 7 hypothermia was indicated.
RESULTS
Perinatal asphyxia occurred in 21.5‰ cases (321/14,896) and HIE in 1.1‰ (16/14,896). The total study population was composed of 281 asphyxiated neonates: 68/5152 (1.3%) born at Hub and 213/9744 (2.2%) at Spokes (p < 0.001, OR 0.59, 95% CI 0.45-0.79). 32/213 (15%) neonates were transferred from Spokes to Hub. Overall, 12/281 were treated with hypothermia. HIE occurred in 16/281 (5.7%) neonates: four grade I, eight grade II and four grade III. Incidence of HIE was not different between Hub and Spokes. Pregnancies resulting in asphyxiated neonates were classified as class 1) 1.1%, 2) 52.3%, 3) 3.2%, and 4) 43.4%. Sentinel events occurred in 23.5% of the cases and FHR was category II or III in 50.5% of the cases. 40.2% cases of asphyxia and 18.8% cases of HIE were not preceded by sentinel events or abnormal FHR.
CONCLUSIONS
We identified at least one risk factor associated with all cases of HIE and with most cases of perinatal asphyxia. In absence of risk factors, the probability of developing perinatal asphyxia resulted extremely low. FHR monitoring alone is not a reliable tool for detecting the probability of eventual asphyxia.
Topics: Apgar Score; Asphyxia Neonatorum; Female; Heart Rate, Fetal; Humans; Hypoxia-Ischemia, Brain; Incidence; Infant; Infant, Newborn; Italy; Male; Pregnancy; Probability; Prospective Studies; Risk Factors
PubMed: 32228514
DOI: 10.1186/s12884-020-02876-1 -
Frontiers in Endocrinology 2023Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants... (Review)
Review
INTRODUCTION
Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children.
RESULTS
Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia.
CONCLUSIONS
Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment.
Topics: Infant, Newborn; Infant; Pregnancy; Female; Child; Humans; Asphyxia; Hypothermia; Parturition; Asphyxia Neonatorum; Endocrine System
PubMed: 37929024
DOI: 10.3389/fendo.2023.1249700 -
Journal of Obstetrics and Gynaecology :... Dec 2023This aim of this study was to investigate maternal hematological laboratory parameters of term infants before birth diagnosed with asphyxia compared to mothers of...
This aim of this study was to investigate maternal hematological laboratory parameters of term infants before birth diagnosed with asphyxia compared to mothers of healthy term infants and predict asphyxia by these parameters. This study was conducted on 109 and 192 mothers of the fetus with asphyxia and healthy, respectively. Laboratory parameters of complete blood count, including PDW (platelet distribution width), PCT (procalcitonin) and NLR (neutrophil/lymphocyte ratio), were recorded before birth from pregnant women. PDW and basophil counts were significantly higher in the asphyxia group than healthy group (: .000). The cut-off level of 19.425 accurately predicted the occurrence of asphyxia (AUC = 0.724 (95% confidence interval 0.65-0.78), = .000). Basophil count could predict asphyxia, especially the cut-off level of> 0.15(10³/μL) (AUC = 0.67) (95% confidence interval 0.60-0.74, = .000). To predict asphyxia before labor, a cheap and routine test of PDW can be used after more research in this area.IMPACT STATEMENT Asphyxia is still an unsolved problem in neonatal mortality and morbidity, and it is seen in babies of mothers who carry some risks during pregnancy (such as multiple pregnancy, baby of mother with preeclampsia, meconium aspiration, diabetes); however, it is known that it is a subject that is still not fully understood as it can also occur as a result of labor that does not have any risk factors and goes well. In term fetuses without risk factors, it can be predicted to a certain extent whether the fetus will be diagnosed with asphyxia from the hemogram test that can work from the blood of the mother before birth. In clinical practice, asphyxia can be estimated with a cheap and simple test, without any extra examination, by looking at the routine blood tests taken from the mother before going into labor.
Topics: Infant; Infant, Newborn; Humans; Pregnancy; Female; Asphyxia; Meconium Aspiration Syndrome; Risk Factors; Asphyxia Neonatorum; Fetus
PubMed: 37051710
DOI: 10.1080/01443615.2023.2199064 -
Seminars in Fetal & Neonatal Medicine Oct 2021Several bedside and laboratory neuromonitoring tools are currently used in neonatal encephalopathy (NE) to assess 1) brain function [amplitude-integrated... (Review)
Review
Several bedside and laboratory neuromonitoring tools are currently used in neonatal encephalopathy (NE) to assess 1) brain function [amplitude-integrated electroencephalogram (aEEG) and EEG], 2) cerebral oxygenation delivery and consumption [near-infrared spectroscopy (NIRS)] and 3) blood and cerebrospinal fluid biomarkers. The aim of the review is to provide the role of neuromonitoring in understanding the development of brain injury in these newborns and better predict their long-term outcome. Simultaneous use of these monitoring modalities may improve our ability to provide meaningful prognostic information regarding ongoing treatments. Evidence will be summarized in this review for each of these modalities, by describing (1) the methods, (2) the clinical evidence in context of NE both before and with hypothermia, and (3) the research and future directions.
Topics: Asphyxia Neonatorum; Brain; Electroencephalography; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Spectroscopy, Near-Infrared
PubMed: 34393094
DOI: 10.1016/j.siny.2021.101273