Neonatal Encephalopathy: Need for Recognition of Multiple Etiologies for Optimal Management

Aslam, Saima; Strickland, Tammy; Molloy, Eleanor J.

doi:10.3389/fped.2019.00142

Cited by 94 publications

(73 citation statements)

References 56 publications

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“…In the study population, hypoglycemia was reported in 4.3% and the presence of infection was reported in 2.0%, both comparable with the general population (5-15% and 4% respectively 24,25 ). The occurrence of bleeding diathesis and encephalopathy in our study population were 8.1% and 3.9% respectively, thus higher than in the general population (2.17-5.9% and 0.3% respectively 26,27 ). The data of this study showed that in 7 of the 47 patients (14.9%) with follow-up, cognitive, and/or motor developmental delay was reported.…”

Section: Phenotypic Spectrumcontrasting

confidence: 55%

Galactokinase deficiency: lessons from the GalNet registry

Rubio‐Gozalbo

Derks

Meyer³

et al. 2021

Genetics in Medicine

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Purpose: Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype. Methods: Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020. Results: Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial. Conclusion: The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed.

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Section: Phenotypic Spectrumcontrasting

confidence: 55%

Galactokinase deficiency: lessons from the GalNet registry

Rubio‐Gozalbo

Derks

Meyer³

et al. 2021

Genetics in Medicine

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“…There is increased risk of neurodevelopmental impairment in infants that experience sepsis and a meta-analysis demonstrated that coagulase-negative staphylococci sepsis in very low birth weight infants is associated with a higher incidence of cerebral palsy (9). Furthermore, infection in preterm infants is associated with a greater incidence of subsequent cardiorespiratory events, such as apnoea and hypoxemia (10), and it is recognized that neonatal encephalopathy is likely multifactorial where both maternal and neonatal infections can exacerbate hypoxic-ischemic (HI) brain injury (11).…”

Section: Introductionmentioning

confidence: 99%

Staphylococcus epidermidis Sensitizes Perinatal Hypoxic-Ischemic Brain Injury in Male but Not Female Mice

et al. 2020

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Background: Staphylococcus epidermidis is the most common nosocomial infection and the predominant pathogen in late-onset sepsis in preterm infants. Infection and inflammation are linked to neurological and developmental sequelae and bacterial infections increase the vulnerability of the brain to hypoxia-ischemia (HI). We thus tested the hypothesis that S. epidermidis exacerbates HI neuropathology in neonatal mice.Methods: Male and female C57Bl/6 mice were injected intraperitoneally with sterile saline or 3.5 × 10 7 colony-forming units of S. epidermidis on postnatal day (PND) 4 and then subjected to HI on PND5 (24 h after injection) or PND9 (5 d after injection) by left carotid artery ligation and exposure to 10% O 2 . White and gray matter injury was assessed on PND14-16. In an additional group of animals, the plasma, brain, and liver were collected on PND5 or PND9 after infection to evaluate cytokine and chemokine profiles, C5a levels and C5 signaling.Results: HI induced 24 h after injection of S. epidermidis resulted in greater gray and white matter injury compared to saline injected controls in males, but not in females. Specifically, males demonstrated increased gray matter injury in the cortex and striatum, and white matter loss in the subcortical region, hippocampal fimbria and striatum. In contrast, there was no potentiation of brain injury when HI occurred 5 d after infection in either sex. In the plasma, S. epidermidis-injected mice demonstrated increased levels of pro-and anti-inflammatory cytokines and chemokines and a reduction of C5a at 24 h, but not 5 d after infection. Brain CCL2 levels were increased in both sexes 24 h after infection, but increased only in males at 5 d post infection.Conclusion: Ongoing S. epidermidis infection combined with neonatal HI increases the vulnerability of the developing brain in male but not in female mice. These sex-dependent effects were to a large extent independent of expression of systemic cytokines or brain CCL2 expression. Overall, we provide new insights into how systemic S. epidermidis infection affects the developing brain and show that the time interval between infection and HI is a critical sensitizing factor in males.

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“…Vol:. (1234567890) Scientific RepoRtS | (2020) 10:13100 | https://doi.org/10.1038/s41598-020-70131-w www.nature.com/scientificreports/ inflammation, infection, metabolic and genetic causes, although these may be clinically indistinguishable 5 . These difficulties have hindered the development of novel neuroprotective strategies.…”

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confidence: 99%

Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy

Montaldo

Cunnington

Oliveira

et al. 2020

Sci Rep

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A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855 genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1 and SMC4 were the most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatonin and polo-like kinase in babies with adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanisms and identify novel therapeutic targets for neuroprotection. Neonatal encephalopathy (NE) related to perinatal asphyxia is the most common cause of death and neurodisability in term babies with an incidence of 2 to 3 per 1,000 live births in high-income countries, and 10 to 20 per 1,000 livebirths in low and middle-income countries 1,2. In high income countries, therapeutic hypothermia partially improves outcomes, although adverse outcomes still occur in up to 30% of the cooled infants 3. As the underlying brain injury evolves over hours and days after birth, early identification of at-risk encephalopathic infants is challenging and often inaccurate, particularly in cooled infants 4. Furthermore, NE is heterogenous condition resulting from a multitude of aetiologies including acute or sub-acute perinatal hypoxia,

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Neonatal Encephalopathy: Need for Recognition of Multiple Etiologies for Optimal Management

Cited by 94 publications

References 56 publications

Galactokinase deficiency: lessons from the GalNet registry

Galactokinase deficiency: lessons from the GalNet registry

Staphylococcus epidermidis Sensitizes Perinatal Hypoxic-Ischemic Brain Injury in Male but Not Female Mice

Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy

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