Cited by 1,070Pregnancy and preeclampsia studiesBirth, Development, and HealthReproductive System and Pregnancy

Pathophysiology of placental-derived fetal growth restriction

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Burton, Graham J., Jauniaux, Eric·2018·American Journal of Obstetrics and Gynecology

Abstract

Placental-related fetal growth restriction arises primarily due to deficient remodeling of the uterine spiral arteries supplying the placenta during early pregnancy. The resultant malperfusion induces cell stress within the placental tissues, leading to selective suppression of protein synthesis and reduced cell proliferation. These effects are compounded in more severe cases by increased infarction and fibrin deposition. Consequently, there is a reduction in villous volume and surface area for maternal-fetal exchange. Extensive dysregulation of imprinted and nonimprinted gene expression occurs, affecting placental transport, endocrine, metabolic, and immune functions. Secondary changes involving dedifferentiation of smooth muscle cells surrounding the fetal arteries within placental stem villi correlate with absent or reversed end-diastolic umbilical artery blood flow, and with a reduction in birthweight. Many of the morphological changes, principally the intraplacental vascular lesions, can be imaged using ultrasound or magnetic resonance imaging scanning, enabling their development and progression to be followed in vivo. The changes are more severe in cases of growth restriction associated with preeclampsia compared to those with growth restriction alone, consistent with the greater degree of maternal vasculopathy reported in the former and more extensive macroscopic placental damage including infarcts, extensive fibrin deposition and microscopic villous developmental defects, atherosis of the spiral arteries, and noninfectious villitis. The higher level of stress may activate proinflammatory and apoptotic pathways within the syncytiotrophoblast, releasing factors that cause the maternal endothelial cell activation that distinguishes between the 2 conditions. Congenital anomalies of the umbilical cord and placental shape are the only placental-related conditions that are not associated with maldevelopment of the uteroplacental circulation, and their impact on fetal growth is limited.

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Crossref · 10.1016/j.ajog.2017.11.577

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Research works printed but not linked: 2

  1. Falco ML, Sivanathan J, Laoreti A, Thilaganathan B, Khalil A. Placental histopa- thology associated with preeclampsia: a sys- tematic review and meta-analysis. Ultrasound Obstet Gynecol 2017;50:295-301.
  2. Xu C, Bailly-Maitre B, Reed JC. Endo- plasmic reticulum stress: cell life and death de- cisions. J Clin Invest 2005;115:2656-64.

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Authors
Burton, G. J., & Jauniaux, E.
Affiliations
  • University of Cambridge (GB)
  • University College London (GB)
Corresponding author
Burton, Graham J.
Venue
American Journal of Obstetrics and Gynecology
Publisher
Elsevier BV
Published
2018-02
Volume
218
Issue
2
Pages
S745-S761
ISSN
0002-9378 (ISSN-L)
OpenAlex
W2792956190
Cited by
1,070
References
182
Citations by year
2026: 179 · 2025: 130 · 2024: 149 · 2023: 171 · 2022: 138 · 2021: 120 · 2020: 111 · 2019: 49 · 2018: 21
FWCI
12.30
Type
journal article
Language
en
Open access
Locations
  • American Journal of Obstetrics and Gynecology (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
placental growth restriction, uteroplacental circulation, spiral artery remodeling, placental malperfusion, placental infarction, fibrin deposition, imprinted gene expression, umbilical artery blood flow, preeclampsia, syncytiotrophoblast, endothelial activation, placental MRI
MeSH terms
Chorionic Villi, Female, Fetal Growth Retardation, Gene Expression Regulation, Humans, Magnetic Resonance Imaging, Maternal-Fetal Exchange, Placenta, Placental Insufficiency, Placentation, Pre-Eclampsia, Pregnancy, Stress, Physiological, Trophoblasts, Umbilical Arteries, Ultrasonography, Prenatal, Genomic Imprinting, Placental Circulation, Uterine Artery, Vascular Remodeling

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