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The Impact of an Adverse Intrauterine Environment on Neurodevelopment

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Neurodevelopmental Pediatrics

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Abstract

This chapter examines the impact of intrauterine conditions and an adverse intrauterine environment on neurodevelopment, with a specific focus on inflammation. Notably, chorioamnionitis, hypoxia-ischemia, placental insufficiency, and certain toxins, such as opioids and alcohol, can catalyze a pro-inflammatory intrauterine microenvironment and facilitate inflammatory signal transduction through the maternal–placental–fetal brain axis. Both molecular and cellular inflammatory mediators play essential roles in the pathophysiology of perinatal brain injury, and can confer damage to the developing central nervous system. In addition to causing direct injury, these mediators, including activated immune cells, chemokines, and cytokines, are key to priming the developing immune system and contributing to immune cell memory, potentially resulting in aberrant neural-immune signaling and exaggerated responses to subsequent inflammatory stimuli later in life. Indeed, this sustained immune hyperreactivity leaves both the immature brain and immune system vulnerable over extended developmental periods. Primary sequelae of severe and persistent intrauterine inflammation can manifest as a broad spectrum of perinatal brain injury, with the increased incidence of cerebral palsy, deficits of cognition, and neuropsychiatric conditions. While specific, targeted therapies remain elusive, emerging interventions aimed at neurorepair and neurorestoration may combat the brain injury associated with preterm birth and other conditions associated with robust intrauterine and perinatal inflammation.

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Abbreviations

AIUI:

Ascending Intrauterine Inflammation

AP-1:

activator protein 1

BBB:

blood–brain barrier

CCL:

C-C motif ligand chemokine

CD:

cluster of differentiation

CHORIO:

chorioamnionitis

CNS:

central nervous system

Cox:

cyclooxygenase

CP:

cerebral palsy

CRP:

C-reactive protein

CXCL:

C-X-C motif ligand chemokine

CXCR:

C-X-C motif chemokine receptor

DAMPS:

Damage-Associated Molecular Patterns

FIRS:

fetal inflammatory response syndrome

HI:

hypoxia-ischemia

HIE:

hypoxic ischemic encephalopathy

IFN:

gamma- interferon gamma

IL:

interleukin

IUGR:

Intrauterine growth restriction

IVH:

intraventricular hemorrhage

LPS:

lipopolysaccharide

MCP-1:

monocyte chemoattractant protein-1

MHC:

major histocompatibility complex

MMP:

matrix metalloproteinase

MPO:

myeloperoxidase

NF-kB:

nuclear factor kappa-light-chain-enhancer of activated B cells

OPC:

oligodendrocyte progenitor cell

P:

postnatal

PBI:

perinatal brain injury

PBMC:

peripheral blood mononuclear cell

PHHP:

posthemorrhagic hydrocephalus of prematurity

PMN:

polymorphonuclear leukocytes

Poly(I:C):

 Polyinosinic:polycytidylic acid

RANTES:

regulated on activation, normal T cell expressed and secreted

SIRS:

systemic inflammatory response syndrome

SPIHR:

sustained peripheral immune hyperreactivity

STAT:

signal transducer and activator of transcription

TLR:

toll-like receptor

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Sindhu Ramachandra, Michelle Low, Nethra Madurai, Maide Ozen, Yuma Kitase, Shenandoah Robinson & Lauren L. Jantzie

  2. Departments of Neurology and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Sindhu Ramachandra, Michelle Low, Nethra Madurai, Maide Ozen, Yuma Kitase, Shenandoah Robinson & Lauren L. Jantzie

  3. Kennedy Krieger Institute, Baltimore, MD, USA

    Sindhu Ramachandra, Michelle Low, Nethra Madurai, Maide Ozen, Yuma Kitase, Shenandoah Robinson & Lauren L. Jantzie

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  1. Sindhu Ramachandra
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  2. Michelle Low
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Correspondence to Lauren L. Jantzie .

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Editors and Affiliations

  1. Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia

    David D. Eisenstat

  2. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

    Dan Goldowitz

  3. Department of Pediatrics and School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

    Tim F. Oberlander

  4. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

    Jerome Y. Yager

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Ramachandra, S. et al. (2023). The Impact of an Adverse Intrauterine Environment on Neurodevelopment. In: Eisenstat, D.D., Goldowitz, D., Oberlander, T.F., Yager, J.Y. (eds) Neurodevelopmental Pediatrics. Springer, Cham. https://doi.org/10.1007/978-3-031-20792-1_9

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