In clinical practice, cerebral MRI in newborns is highly predictive of neurodevelopmental outcome after therapeutic hypothermia

Tharmapoopathy, Pavithira; Chisholm, Philippa; Barlas, Akif; Varsami, Marianna; Gupta, Neelam; Ekitzidou, Georgia; Ponnusamy, Vennila; Kappelou, Olga; Evanson, Jane; Rosser, Gabriel; Shah, Divyen K.

doi:10.1016/j.ejpn.2019.12.018

Cited by 17 publications

(19 citation statements)

References 23 publications

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“…Neonates in Group 1 (moderate to severe NE with TH) had a signi cantly lower Apgar score at 10 min, were more likely to require respiratory support and need chest compressions compared to those in Group 2 (mild NE without TH) as shown in Table 1. We have shown that there was a strong correlation between MRI outcome and two-year neurodevelopmental outcome in this cohort 16 . Of the neonates with moderate to severe NE treated with TH, all those in the favourable MRI group had a normal neurodevelopmental outcome as opposed to only one in the unfavourable MRI group at a median age of 2.5 years.…”

Section: Validation Of Control and Candidate Mirnas Through Rt-qpcrsupporting

confidence: 50%

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Novel mechanism of action for neuronal let-7b-5p in neonatal encephalopathy through the Hippo pathway

Ponnusamy

Mohamed

et al. 2021

Preprint

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Despite increasing knowledge on microRNAs, their role in the pathogenesis of neonatal encephalopathy remains to be elucidated. Herein, we identify let-7b-5p as a significant microRNA in neonates with moderate to severe encephalopathy from the dried blood spots using unbiased microRNA next generation sequencing. Validation studies using Reverse Transcription and quantitative Polymerase Chain Reaction on 45 neonates showed that let-7b-5p expression was increased on day 1 in neonates with moderate to severe encephalopathy with unfavourable outcome when compared to those with mild encephalopathy. Mechanistic studies performed on glucose deprived cell cultures and the cerebral cortex of two animal models of perinatal brain injury, namely hypoxic-ischaemic and intrauterine inflammation models confirm that let-7b-5p is associated with the apoptotic Hippo pathway. Significant reduction in neuronal let-7b-5p expression corresponded with activated Hippo pathway, with increased neuronal/nuclear ratio of Yes Associated Protein (YAP) and increased neuronal cleaved caspase-3 expression in both animal models. Similar results were noted for let-7b-5p and YAP expression in glucose-deprived cell cultures. Reduced nuclear YAP with decreased intracellular let-7b-5p correlated with neuronal apoptosis in conditions of metabolic stress. This novel finding of the Hippo-YAP-let-7b axis needs validation in larger cohorts and other models to further our knowledge on let-7b-5p as a biomarker for neonatal encephalopathy.

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Section: Validation Of Control and Candidate Mirnas Through Rt-qpcrsupporting

confidence: 50%

“…Group 3 were cord blood samples from normal pregnancies. Neonates in Group 1 treated with TH were further divided into 2 subgroups: those with cerebral MRI predictive of either favourable (Group 1A) or unfavourable outcome (Group 1B), based on a validated scoring system 42 as previously described 16 .…”

Section: Discussionmentioning

confidence: 99%

Novel mechanism of action for neuronal let-7b-5p in neonatal encephalopathy through the Hippo pathway

Ponnusamy

Mohamed

et al. 2021

Preprint

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“…also found neonatal factors to have the overall strongest associations with CP and neonatal seizures to be the most pronounced risk factor 21 . Therapeutic hypothermia is, unsurprisingly, highly associated with CP, since the indication for this treatment is birth asphyxia combined with encephalopathy as a sign of substantial brain injury 27 . However, when adjusting for the covariables leading to the treatment, the increased risk disappears and perhaps we would have found a protective effect with a bigger sample size.…”

Section: Discussionmentioning

confidence: 73%

“…21 Therapeutic hypothermia is, unsurprisingly, highly associated with CP, since the indication for this treatment is birth asphyxia combined with encephalopathy as a sign of substantial brain injury. 27 However, when adjusting for the covariables leading to the treatment, the increased risk disappears and perhaps we would have found a protective effect with a bigger sample size. Similarly, the other included neonatal treatments all have increased associations with CP, even though we would expect them to be protective, and this is likely also a matter of confounding by indication due to uncontrolled covariables.…”

Section: Discussionmentioning

confidence: 78%

Declining prevalence of cerebral palsy in children born at term in Denmark

Larsen

Rackauskaite

Greisen

et al. 2021

Develop Med Child Neuro

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Aim To investigate reasons for the declining prevalence of cerebral palsy (CP) in children born at term in Denmark by evaluating obstetric and neonatal factors associated with CP, and their changes over time. Method In this cohort study, we included 987 495 children (504 600 [51.1%] males and 482 895 [48.9%] females) born after 37 completed gestational weeks during birth years 1997 to 2013. Risk ratios of CP for each factor were calculated with log‐binominal regression analyses. Significant factors were evaluated concerning their development in prevalence over time. Results In the antenatal period, there were significant associations with an increased risk of CP and high maternal body mass index (BMI), smoking during pregnancy, nulliparity, male sex, gestational age, and low birthweight. In the study period, fewer females smoked during pregnancy and fewer children were born post‐term, dropping from 22.6% to 11.4% and 9.4% to 2.5% respectively. Conversely, the proportion of females with high BMI increased. Most significant risk factors were found in the neonatal period, with an increase in children with diagnosed birth defects and children admitted to neonatal care. Interpretation Reasons for the declining prevalence of CP appear to be multifactorial and likely include the decline in maternal smoking and children born post‐term along with centralization and advances in neonatal treatment.

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“…Of the moderatesevere HIE group, eight (17%) newborns had cerebral MRI predictive of an unfavourable outcome [31]. The rating of the MR images was described previously in this cohort [32] using a validated system [31].…”

Section: Patients and Samplesmentioning

confidence: 99%

Lipid Profiles from Dried Blood Spots Reveal Lipidomic Signatures of Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy

Nixon

Jenkins

et al. 2021

Nutrients

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Hypoxic-ischemic encephalopathy (HIE) is associated with perinatal brain injury, which may lead to disability or death. As the brain is a lipid-rich organ, various lipid species can be significantly impacted by HIE and these correlate with specific changes to the lipidomic profile in the circulation. Objective: To investigate the peripheral blood lipidomic signature in dried blood spots (DBS) from newborns with HIE. Using univariate analysis, multivariate analysis and sPLS-DA modelling, we show that newborns with moderate–severe HIE (n = 46) who underwent therapeutic hypothermia (TH) displayed a robust peripheral blood lipidomic signature comprising 29 lipid species in four lipid classes; namely phosphatidylcholine (PC), lysophosphatidylcholine (LPC), triglyceride (TG) and sphingomyelin (SM) when compared with newborns with mild HIE (n = 18). In sPLS-DA modelling, the three most discriminant lipid species were TG 50:3, TG 54:5, and PC 36:5. We report a reduction in plasma TG and SM and an increase in plasma PC and LPC species during the course of TH in newborns with moderate–severe HIE, compared to a single specimen from newborns with mild HIE. These findings may guide the research in nutrition-based intervention strategies after HIE in synergy with TH to enhance neuroprotection.

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In clinical practice, cerebral MRI in newborns is highly predictive of neurodevelopmental outcome after therapeutic hypothermia

Cited by 17 publications

References 23 publications

Novel mechanism of action for neuronal let-7b-5p in neonatal encephalopathy through the Hippo pathway

Novel mechanism of action for neuronal let-7b-5p in neonatal encephalopathy through the Hippo pathway

Declining prevalence of cerebral palsy in children born at term in Denmark

Lipid Profiles from Dried Blood Spots Reveal Lipidomic Signatures of Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy

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