Cited by 620Pregnancy and preeclampsia studiesNeonatal and fetal brain pathologyBirth, Development, and Health

The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome

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Miller, Suzanne L., Huppi, Petra S., Mallard, Carina·2016·The Journal of Physiology

Abstract

Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3–9% of pregnancies in high‐income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing . Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth‐restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long‐range connections. Subsequent to these structural alterations, short‐ and long‐term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions. image

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  • Intrauterine growth restriction, low birth weight and reduced fetal viability, including stunted growth and cognitive development in children, have been observed in association with chronic disease in adulthood.

    “Intrauterine growth restriction, low birth weight and reduced fetal viability, including stunted growth and cognitive development in children, have been observed in association with chronic disease in adulthood [176, 177].”

    From Current update on malaria in pregnancy: a systematic review (2025) · cites this paper as [177]

    The Introduction (page unavailable) links fetal growth restriction with perinatal death and later cognitive and learning impairments, and discusses low birth weight in relation to IQ. It does not support the claim that these outcomes are associated with chronic disease in adulthood; the passages found about adulthood concern intellectual performance or neurological outcomes, not chronic disease. (LLM, conf=0.87)

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Authors
Miller, S. L., Huppi, P. S., & Mallard, C.
Affiliations
  • The Ritchie Centre Hudson Institute of Medical Research and The Department of Obstetrics and Gynaecology Monash University Clayton Victoria Australia
  • Division of Development and Growth Department of Pediatrics University of Geneva Switzerland
  • University of Gothenburg (SE)
Venue
The Journal of Physiology
Publisher
Wiley
Published
2016-01-05
Volume
594
Issue
4
Pages
807-823
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
OpenAlex
W2176374714
Cited by
620
References
140
Citations by year
2026: 63 · 2025: 77 · 2024: 73 · 2023: 83 · 2022: 74 · 2021: 67 · 2020: 56 · 2019: 59 · 2018: 29 · 2017: 28 · 2016: 9 · 2015: 1
FWCI
3.30
Type
journal article
Language
en
Open access
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
fetal growth restriction, brain sparing, fetal hypoxia, placental insufficiency, neurodevelopmental outcomes, brain structure, cortical volume, myelination, brain connectivity, neuronal migration, gestational age at delivery, perinatal mortality, motor and cognitive deficits
MeSH terms
Animals, Brain, Female, Fetal Growth Retardation, Humans, Pregnancy

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