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Ibrain 2023Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the important complications of neonatal asphyxia, which not only leads to neurological disability but also... (Review)
Review
Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the important complications of neonatal asphyxia, which not only leads to neurological disability but also seriously threatens the life of neonates. Over the years, animal models of HIE have been a research hotspot to find ways to cope with HIE and thereby reduce the risk of neonatal death or disability in moderate-to-severe HIE. By reviewing the literature related to HIE over the years, it was found that nonhuman primates share a high degree of homology with human gross neural anatomy. The basic data on nonhuman primates are not yet complete, so it is urgent to mine and develop new nonhuman primate model data. In recent years, the research on nonhuman primate HIE models has been gradually enriched and the content is more novel. Therefore, the purpose of this review is to further summarize the methods for establishing the nonhuman primate HIE model and to better elucidate the relevance of the nonhuman primate model to humans by observing the behavioral manifestations, neuropathology, and a series of biomarkers of HIE in primates HIE. Finally, the most popular and desirable treatments studied in nonhuman primate models in the past 5 years are summarized.
PubMed: 37786551
DOI: 10.1002/ibra.12097 -
EBioMedicine Aug 2023Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong... (Observational Study)
Observational Study
BACKGROUND
Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO and temperature during TH.
METHODS
This was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15).
FINDINGS
Data quality for 58 neonates was sufficient for analysis. CMRO changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO at NT was positively associated with cognitive and motor composite scores (β (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10 moL/dl × mm/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes.
INTERPRETATION
Point of care measures of CMRO in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE.
FUNDING
This clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).
Topics: Infant, Newborn; Infant; Pregnancy; Humans; Female; Young Adult; Adult; Cohort Studies; Prospective Studies; Hypoxia-Ischemia, Brain; Infant, Newborn, Diseases; Oxygen; Hypothermia, Induced
PubMed: 37392599
DOI: 10.1016/j.ebiom.2023.104673 -
BMC Pregnancy and Childbirth Aug 2023Birth asphyxia is of significant concern because it impacts newborn health from low to severe levels. In Thailand, birth asphyxia remains a leading cause of delayed...
BACKGROUND
Birth asphyxia is of significant concern because it impacts newborn health from low to severe levels. In Thailand, birth asphyxia remains a leading cause of delayed developmental health in children under 5 years old. The study aimed to determine the maternal, fetal and health service factors contributing to birth asphyxia.
METHODS
A case-control design was conducted on a sample of 4256 intrapartum chart records. The samples were selected based on their Apgar scores in the first minute of life. A low Apgar score (≤ 7) was chosen for the case group (852) and a high Apgar score (> 7) for the control group (3408). In addition, a systematic random technique was performed to select 23 hospitals, including university, advanced and secondary, in eight health administration areas in Thailand for evaluating the intrapartum care service. Data analysis was conducted using SPSS statistical software.
RESULTS
The odds of birth asphyxia increases in the university and advanced hospitals but the university hospitals had the highest quality of care. The advanced and secondary hospitals had average nurse work-hours per week of more than 40 h. Multivariable logistic regression analysis found that intrapartum care services and maternal-fetal factors contributed to birth asphyxia. The odd of birth asphyxia increases significantly in late-preterm, late-term pregnancies, low-birth weight, and macrosomia. Furthermore, maternal comorbidity, non-reassuring, and obstetric emergency conditions significantly increase the odd of birth asphyxia. In addition, an excellent quality of intrapartum care, a combined nursing model, low nurse work-hours, and obstetrician-conducted delivery significantly reduced birth asphyxia.
CONCLUSION
Birth asphyxia problems may be resolved in the health service management offered by reducing the nurse work-hours. Excellent quality of care required the primary nursing care model combined with a team nursing care model. However, careful evaluation and monitoring are needed in cases of comorbidity, late-preterm, late-term pregnancies, low-birth weight, and macrosomia. Furthermore, increasing the obstetrician availability in obstetric emergencies and non-reassuring fetal status is important.
Topics: Child, Preschool; Female; Humans; Infant, Newborn; Pregnancy; Apgar Score; Asphyxia; Asphyxia Neonatorum; Birth Weight; Case-Control Studies; Fetal Macrosomia; Hospitals, University; Risk Factors; Thailand
PubMed: 37582743
DOI: 10.1186/s12884-023-05885-y -
Neonatology 2024The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or...
OBJECTIVES
The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE.
STUDY DESIGN
In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers.
RESULTS
GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681-0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases.
CONCLUSIONS
Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III.
Topics: Infant; Humans; Infant, Newborn; Case-Control Studies; Interleukin-6; Asphyxia; Hypoxia-Ischemia, Brain; Fetal Blood; Biomarkers; Cytokines; Asphyxia Neonatorum
PubMed: 37778335
DOI: 10.1159/000533473 -
PloS One 2023In low-resource settings, it is challenging to ascertain the burden and causes of under-5 mortality as many deaths occur outside health facilities. We aimed to determine...
BACKGROUND
In low-resource settings, it is challenging to ascertain the burden and causes of under-5 mortality as many deaths occur outside health facilities. We aimed to determine the causes of childhood deaths in rural Gambia using verbal autopsies (VA).
METHODOLOGY
We used WHO VA questionnaires to conduct VAs for deaths under-5 years of age in the Basse and Fuladu West Health and Demographic Surveillance Systems (HDSS) in rural Gambia between September 01, 2019, and December 31, 2021. Using a standardized cause of death list, two physicians assigned causes of death and discordant diagnoses were resolved by consensus.
RESULTS
VAs were conducted for 89% (647/727) of deaths. Of these deaths, 49.5% (n = 319) occurred at home, 50.1% (n = 324) in females, and 32.3% (n = 209) in neonates. Acute respiratory infection including pneumonia (ARIP) (33.7%, n = 137) and diarrhoeal diseases (23.3%, n = 95) were the commonest primary causes of death in the post-neonatal period. In the neonatal period, unspecified perinatal causes of death (34.0%, n = 71) and deaths due to birth asphyxia (27.3%, n = 57) were the commonest causes of death. Severe malnutrition (28.6%, n = 185) was the commonest underlying cause of death. In the neonatal period, deaths due to birth asphyxia (p-value<0.001) and severe anaemia (p-value = 0.03) were more likely to occur at hospitals while unspecified perinatal deaths (p-value = 0.01) were more likely to occur at home. In the post-neonatal period, deaths due to ARIP (p-value = 0.04) and diarrhoeal disease (p-value = 0.001) were more likely to occur among children aged 1-11 months and 12-23 months respectively.
CONCLUSION
According to VA analysis of deaths identified within two HDSS in rural Gambia, half of deaths amongst children under-5 in rural Gambia occur at home. ARIP and diarrhoea, and the underlying cause of severe malnutrition remain the predominant causes of child mortality. Improved health care and health-seeking behaviour may reduce childhood deaths in rural Gambia.
Topics: Child; Infant, Newborn; Female; Pregnancy; Humans; Infant; Autopsy; Cause of Death; Gambia; Asphyxia; Respiratory Tract Infections; Protein-Energy Malnutrition; Diarrhea
PubMed: 37410741
DOI: 10.1371/journal.pone.0277377 -
Frontiers in Pharmacology 2024Ticagrelor is a commonly used antiplatelet agent, but due to the stringent criteria for trial population inclusion and the limited sample size, its safety profile has...
BACKGROUND
Ticagrelor is a commonly used antiplatelet agent, but due to the stringent criteria for trial population inclusion and the limited sample size, its safety profile has not been fully elucidated.
METHOD
We utilized OpenVigil 2.1 to query the FDA Adverse Event Reporting System database and retrieved reports by the generic name "ticagrelor" published between 1 October 2010 and 31 March 2023. Adverse drug events (ADEs) were classified and described according to the preferred terms and system organ classes in the Medical Dictionary of Regulatory Activity. Proportional reporting ratio (PRR), reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were used to detect signals.
RESULTS
The number of ADE reports with ticagrelor as the primary suspect drug was 12,909. The top three ADEs were dyspnea [1824 reports, ROR 7.34, PRR 6.45, information component (IC) 2.68], chest pain (458 reports, ROR 5.43, PRR 5.27, IC 2.39), and vascular stent thrombosis (406 reports, ROR 409.53, PRR 396.68, IC 8.02). The highest ROR, 630.24, was found for "vascular stent occlusion". Cardiac arrest (137 reports, ROR 3.41, PRR 3.39, IC 1.75), atrial fibrillation (99 reports, ROR 2.05, PRR 2.04, IC 1.03), asphyxia (101 reports, ROR 23.60, PRR 23.43, IC 4.51), and rhabdomyolysis (57 reports, ROR 2.75, PRR 2.75, IC 1.45) were suspected new adverse events of ticagrelor.
CONCLUSION
The FAERS database produced potential signals associated with ticagrelor that have not been recorded in the package inserts, such as cardiac arrest, atrial fibrillation, asphyxia, and rhabdomyolysis. Further clinical surveillance is needed to quantify and validate potential hazards associated with ticagrelor-related adverse events.
PubMed: 38655177
DOI: 10.3389/fphar.2024.1251961 -
European Journal of Paediatric... Nov 2023To describe longitudinal motor development in children treated with therapeutic- hypothermia (TH) due to neonatal hypoxic-ischaemic encephalopathy (HIE) and to explore...
AIMS
To describe longitudinal motor development in children treated with therapeutic- hypothermia (TH) due to neonatal hypoxic-ischaemic encephalopathy (HIE) and to explore motor functioning in early adolescence.
MATERIAL AND METHODS
Children treated with TH due to HIE during 2007-2009, in Stockholm, participated in a prospective follow-up study. Motor development was assessed on four occasions, reported as percentiles and at mean ages. Alberta Infant Motor Scale was used at 0.35 years of age, Bayley Scales of Infant and Toddler Development-III at 2.1 years and Movement Assessment Battery for Children (MABC-2) at 7.3 and 11.1 years of age. MABC-2 Checklist was completed by parents at 7.3 and 11.1 years of age. General cognition was assessed using Wechsler Intelligence Scales for Children Fifth Edition (WISC-V).
RESULTS
Thirty-one percent (14/45) of the children had a motor score ≤ 15 percentile, indicating risk of motor difficulties at 11.1 years of age, and simultaneously the scores from parents of 52% (23/44), indicating risk of motor difficulties in the everyday context. These children had significantly lower motor percentile at 2.1 years of age, but within the normal range. Longitudinal motor development displayed a weak association with WISC-V Full Scale IQ (r0.38, p = 0.013).
CONCLUSION
Among survivors of hypothermia-treated HIE free of moderate/severe cerebral palsy, a third had MABC-2 scores indicating risk of motor difficulties at 11.1 years of age. As motor difficulties became more apparent over time, we suggest that children treated with TH due to neonatal HIE should be followed into at least middle school age.
Topics: Infant, Newborn; Infant; Humans; Child, Preschool; Follow-Up Studies; Prospective Studies; Hypoxia-Ischemia, Brain; Hypothermia; Cerebral Palsy; Hypothermia, Induced
PubMed: 37862884
DOI: 10.1016/j.ejpn.2023.10.003 -
American Journal of Perinatology Sep 2023To investigate the effect of different methods of delivery on the outcome of twin pregnancies.
OBJECTIVE
To investigate the effect of different methods of delivery on the outcome of twin pregnancies.
STUDY DESIGN
This is a retrospective cohort review of 627 twin pregnancies with delivery from January 2016 to December 2019. According to the clinical guidelines for cesarean section, the cesarean section and vaginal delivery groups were determined. Finally, the baseline information, delivery method, pregnancy outcome, and maternal and infant complications of the two groups were compared.
RESULTS
For different delivery methods, the incidence of preeclampsia was significantly higher in the cesarean section group than in the vaginal delivery group ( = 4.405, < 0.05). There were 23 fetal growth ratios (FGR) in the cesarean section group, which were significantly higher than the vaginal delivery group ( = 4.740, < 0.05). However, the incidence of preterm premature rupture of membranes (PPROM) in the vaginal delivery group was significantly higher than in the cesarean section group ( = 5.235, < 0.05). In addition, the volume of postpartum bleeding in the vaginal delivery group was significantly higher than in the cesarean section group ( = 4.723, < 0.001). The neonatal weights and 5-minute Apgar scores of the vaginal delivery group were lower than the cesarean section group, and the difference was statistically significant. In the vaginal delivery group, 48 and 26 neonates were transferred to the intensive care and neonatal units, respectively, which were significantly higher than in the cesarean section group ( = 5.001, < 0.05).
CONCLUSION
The major complications of a twin pregnancy are gestational diabetes mellitus and PPROM. Cesarean section can reduce the rate of neonatal asphyxia in twins and improve the pregnancy outcome.
KEY POINTS
· Twin pregnancy.. · Delivery methods.. · Pregnancy outcomes..
Topics: Infant, Newborn; Pregnancy; Humans; Female; Cesarean Section; Pregnancy, Twin; Retrospective Studies; Delivery, Obstetric; Pregnancy Outcome
PubMed: 34492720
DOI: 10.1055/s-0041-1735492 -
Abnormal expression and role of MicroRNA-214-3p/SLC8A1 in neonatal Hypoxic-Ischaemic encephalopathy.International Journal of Experimental... Aug 2023Neonatal hypoxic-ischaemic encephalopathy (HIE) refers to brain damage caused by intra-uterine distress and asphyxia/hypoxia during the perinatal and neonatal periods....
Neonatal hypoxic-ischaemic encephalopathy (HIE) refers to brain damage caused by intra-uterine distress and asphyxia/hypoxia during the perinatal and neonatal periods. MicroRNA (MiR)-214-3p plays a critical role in cell growth and apoptosis. The aim of this study was to investigate the expression and role of miR-214-3p in neonatal HIE development, and to explore the underlying mechanisms. The expression of miR-214-3p was significantly down-regulated, while that of Slc8a1, a direct target of miR-214-3p, was significantly up-regulated, in the brain tissue of neonatal HIE rats. The over-expression of miR-214-3p promoted the proliferation and inhibited the apoptosis of neurones, while its down-regulation had the opposite effect. Our results indicate that miR-214-3p expression was down-regulated in neonatal HIE rats, and the up-regulation of miR-214-3p expression protected against HIE development by inhibiting neuronal apoptosis.
Topics: Animals; Female; Pregnancy; Rats; Apoptosis; Brain; Down-Regulation; Hypoxia; Hypoxia-Ischemia, Brain; MicroRNAs
PubMed: 37032493
DOI: 10.1111/iep.12475 -
The Journal of Pediatrics Jul 2023To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the...
OBJECTIVE
To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia.
METHODS
This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore. The evolution of brain lesions was assessed, and both scans were related to 18- to 24-month composite outcome. Adverse outcome included cerebral palsy, neurodevelopmental delay, hearing/visual impairment, and epilepsy.
RESULTS
Neonatal DGM injury generally evolved into DGM atrophy and focal signal abnormalities, and WM/watershed injury evolved into WM and/or cortical atrophy. Although the neonatal total and DGM scores were associated with composite adverse outcomes, the 3-month DGM score (OR 1.5, 95% CI 1.2-2.0) and WM score (OR 1.1, 95% CI 1.0-1.3) also were associated with composite adverse outcomes (occurring in n = 23). The 3-month multivariable model (including the DGM and WM subscores) had higher positive (0.88 vs 0.83) but lower negative predictive value (0.83 vs 0.84) than neonatal MRI. Inter-rater agreement for the total, WM, and DGM 3-month score was 0.93, 0.86, and 0.59.
CONCLUSIONS
In particular, DGM abnormalities on 3-month MRI, preceded by DGM abnormalities on the neonatal MRI, were associated with 18- to 24-month outcome, indicating the utility of 3-month MRI for treatment evaluation in neuroprotective trials. However, the clinical usefulness of 3-month MRI seems limited compared with neonatal MRI.
Topics: Infant, Newborn; Pregnancy; Female; Infant; Humans; Retrospective Studies; Asphyxia; Magnetic Resonance Imaging; Infant, Newborn, Diseases; Asphyxia Neonatorum; Brain Injuries; Atrophy; Brain
PubMed: 37019329
DOI: 10.1016/j.jpeds.2023.113402