The long-term effect of perinatal asphyxia on hippocampal volumes

Annink, Kim V.; Vries, Linda S. de; Groenendaal, Floris; Heuvel, Martijn P. van den; Haren, Neeltje E.M. van; Swaab, Hanna; Handel, M; Jongmans, Marian J.; Benders, Manon J. N. L.; Aa, Niek E. van der

doi:10.1038/s41390-018-0115-8

Cited by 39 publications

(33 citation statements)

References 37 publications

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“…In this study, we have demonstrated that this novel and simple prenatal hypoxia protocol recapitulates several key features seen in children born after mild HIE, including deficits in anxiety [59], motor function [60], and susceptibility to seizures [4,58]. These functional deficits occur in the absence of long term structural deficits, which is also consistent with lack of gross anatomic deficits in children with mild HIE [4,61]. Together these data suggest that this model of transient prenatal hypoxia is most similar to mild neurodevelopmental deficits after mild HIE, a clinically important group of patients.…”

Section: Discussion/conclusionsupporting

confidence: 71%

“…Some if these deficits are analogous to neurodevelopmental disabilities seen in children after HIE, including in deficits in anxiety [59], motor function [60], and susceptibility to seizures [4, 61]. The functional deficits in the absence of long-term structural deficits is also consistent with lack of gross anatomic deficits in children with mild HIE [4, 62]. This model did not, however, demonstrate significant deficits in motor learning or visual-spatial learning that would more directly correlate to cognitive deficits sometimes seen in these children [7].…”

Section: Discussion/conclusionmentioning

confidence: 97%

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Deficits in seizure threshold and other behaviors in adult mice without gross neuroanatomic injury after late gestation transient prenatal hypoxia

Cristancho

Gadra²,

Samba³

et al. 2021

Preprint

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Intrauterine hypoxia is a common cause of brain injury in children with a wide spectrum of long-term neurodevelopmental sequela even after milder injury that does not result in significant neuroanatomical injury. Published prenatal hypoxia models generally require many days of modest hypoxia or are invasive, difficult to replicate surgery to ligate the uterine artery. Postnatal models of neonatal hypoxic brain injury are not able to study the effects of antenatal risk factors that contribute to outcomes of hypoxia to the developing brain. In addition, the most common postnatal hypoxia models induce significant cell death and large focal neuroanatomic injury through unilateral ischemia, which is not a common pattern of injury in children. Large animal models suggest that brief transient prenatal hypoxia alone is sufficient to lead to significant functional impairment to the developing brain. Thus, to further understand the mechanisms underlying hypoxic injury to the developing brain, it is vital to develop murine models that are simple to reproduce and phenocopy the lack of neuroanatomic injury but significant functional injury seen in children affected by mild intrauterine hypoxia. Here we characterized the effect of late gestation (embryonic day 17.5) transient prenatal hypoxia on long-term anatomical and neurodevelopmental outcomes. Prenatal hypoxia induced hypoxia inducible factor 1 alpha in the fetal brain. There was no difference in gestational age at birth, litter size at birth, survival, fetal brain cell death, or long-term changes in gray or white matter between offspring after normoxia and hypoxia. However, there were several long-term functional consequences from prenatal hypoxia, including sex-dichotomous changes. Both males and females have abnormalities in repetitive behaviors, hindlimb strength, and decreased seizure threshold. Males demonstrated increased anxiety. Females have deficit in social interaction. Hypoxia did not result in motor or visual learning deficits. This work demonstrates that transient late gestation prenatal hypoxia is a simple, clinically-relevant paradigm for studying putative environmental and genetic modulators of the long-term effects of transient hypoxia on the developing brain.

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Section: Discussion/conclusionsupporting

confidence: 71%

Section: Discussion/conclusionmentioning

confidence: 97%

Deficits in seizure threshold and other behaviors in adult mice without gross neuroanatomic injury after late gestation transient prenatal hypoxia

Cristancho

Gadra²,

Samba³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Thus, perinatal hypoxia has been shown to account for the subsequent profile of long-term cognitive impairment in the general population 45 . For example, one study showed that compared to controls, children with perinatal asphyxia had smaller hippocampal volumes that were associated with poorer long-term visuospatial memory 46 . Another study showed that even mild oxygen deprivation at, or immediately after, birth was related to an increased risk of developmental delays later in childhood: those with mild to moderate acidosis (a measure of risk of hypoxia) displayed significantly lower (p < 0.05) verbal and visuospatial test scores than the low-risk group 47 .…”

Section: Introductionmentioning

confidence: 99%

Relationship between Apgar scores and long-term cognitive outcomes in individuals with Down syndrome

Soriano

Rosser

Hamilton

et al. 2021

Sci Rep

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This study examined the contribution of the Apgar score at 1 and 5 min after birth to later cognitive functioning in 168 individuals with Down syndrome who were between 6 and 25 years of age at time of cognitive testing. Our results showed that a lower Apgar score at 1 min was related to a worse performance in later cognitive measures of receptive vocabulary, verbal comprehension and production, visual memory and working memory. Results also showed that a lower Apgar score at 5 min was only related to worse later outcomes of verbal comprehension and production and auditory working memory. Our findings suggest a need for future studies investigating how specific perinatal events reflected in the Apgar score are linked to later cognitive functioning in individuals with Down syndrome.

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“…In the Netherlands, infants with HIE are currently followed in the outpatient clinics until 5.5 years of age. As shown in this thesis and by others, some deficits, such as memory problems or behavioral problems, only become evident at school-age (1,(30)(31)(32)66,67).…”

Section: Long-term Follow-upmentioning

confidence: 55%

“…According to a growing number of studies, 7.0T MRI enables better visualization of micro-bleedings and the microcirculation at SWI, MRA and MRV, detection of additional metabolites at MRS and better quality of T2-weighted imaging that allows to see more details of the anatomy i.e. the different layers of the cortex can be distinguished (66). In infants 7.0T MRI might also be beneficial to optimize MRI quality, but so far this has never been performed.…”

Section: Innovative Neuroimaging Methodsmentioning

confidence: 99%

Perinatal Asphyxia: Predicting and Improving Outcome

Annink¹

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All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without prior written admission from the author. The copyright of the papers that have been published or have been accepted for publication has been transferred to the respective journals. Als je een schip wilt bouwen, beveel anderen dan niet om hout te verzamelen, het werk te verdelen en orders te geven. In plaats daarvan, leer ze verlangen naar de enorme, eindeloze zee. Antoine de Saint-Exupé TABLE OF CONTENTS Chapter 1 General introduction p. Part I: neuroimaging and follow-up Chapter 2 Uneven distribution of Purkinje cell injury in the cerebellar vermis of term neonates with hypoxic-ischemic encephalopathy p. Chapter 3 Cerebellar injury in term neonates with hypoxic-ischemic encephalopathy is underestimated with antemortem diffusion weighted MRI in comparison to postmortem histopathology p. Chapter 4 General introduction 14.

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The long-term effect of perinatal asphyxia on hippocampal volumes

Abstract: Children with moderate HIE had smaller hippocampal volumes than controls, with a trend toward smaller volumes following mild HIE. Reduced hippocampal volumes were associated with poorer long-term visuospatial memory.

Cited by 39 publications

References 37 publications

Deficits in seizure threshold and other behaviors in adult mice without gross neuroanatomic injury after late gestation transient prenatal hypoxia

Deficits in seizure threshold and other behaviors in adult mice without gross neuroanatomic injury after late gestation transient prenatal hypoxia

Relationship between Apgar scores and long-term cognitive outcomes in individuals with Down syndrome

Perinatal Asphyxia: Predicting and Improving Outcome

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