High-altitude hypoxia and preeclampsia

Zamudio, Stacy

doi:10.2741/2286

Cited by 97Pregnancy and preeclampsia studiesHigh Altitude and HypoxiaNeurological Complications and Syndromes

High-altitude hypoxia and preeclampsia

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Zamudio, Stacy·2007·Frontiers in Bioscience

DOI 10.2741/2286PMC PMC6428070

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Abstract

The influence of hypoxia (lowered arterial blood and/or tissue PO2) on fetoplacental development and the role of hypoxia in preeclampsia are major research foci in perinatal biology. While animal and cell models are of utility, we do not know whether artificial hypoxic stimuli mimic the pathological conditions attributed to hypoxic stress in vivo; we cannot distinguish the effects of hypoxia from under- or overlying pathologies. High altitude (>2700 m) is the natural experiment we can use to distinguish pathology from adaptation in human pregnancy. The two best known impacts of high altitude on pregnancy outcome are reduced fetal growth and an increased incidence preeclampsia. This review focuses on the mechanisms by which altitude increases maternal risk for the development of preeclampsia. The review first considers the evidence that placental hypoxia is causally involved in the development of preeclampsia. It then focuses on how data from studies of pregnant women at high altitude support (or do not support) etiological models of preeclampsia. Considered are the theories that reduced uteroplacental blood flow, circulating factors of placental origin, placental oxidative stress and increased maternal vascular reactivity are etiological in preeclampsia. The data suggest that oxidative stress and endothelial dysfunction have pathophysiological origins that are independent of placental hypoxia. We conclude that altitude shifts the individual risk for the development of preeclampsia because of impacts on multiple physiological systems, no one of which can be specifically pointed to as causal.

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PE should be more prevalent at high altitude, and this prediction is borne out.
“one prediction, that is borne out [487,530], is that PE should therefore be more prevalent at high altitude.”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [487]

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Sympatho‐adrenal and cardiovascular reactivity in pregnancy‐induced hypertension. I. Responses to isometric exercise and a cold pressor test
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Remodelling of Uteroplacental Arteries is Decreased in High Altitude Placentae
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Enhanced Protein Levels of Protein Thiol/Disulphide Oxidoreductases in Placentae from Pre-eclamptic subjects
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Observations on the mono-amine oxidase activity of placenta and uterus
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Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia
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VASCULAR REACTIVITY AND ELECTROLYTES IN NORMAL AND TOXEMIC PREGNANCY PATHOGENIC CONSIDERATIONS AND A DIAGNOSTIC PRE-TOXEMIA TEST*
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Autonomic Imbalance in Preeclampsia: Evidence for Increased Sympathetic Tone in Response to the Supine-Pressor Test
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Mechanisms of Shear Stress-Induced Endothelial Nitric-Oxide Synthase Phosphorylation and Expression in Ovine Fetoplacental Artery Endothelial Cells1
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Effects of Pulsatile Shear Stress on Nitric Oxide Production and Endothelial Cell Nitric Oxide Synthase Expression by Ovine Fetoplacental Artery Endothelial Cells1
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Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow
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Sympathoadrenal and cardiovascular reactivity in pregnancy-induced hypertension
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Differential levels of T helper cytokines in preeclampsia, pregnancy, labor and puerperium
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Quantitative differences in arterial morphometry define the placental bed in preeclampsia
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Expression of Thrombin Receptors in Endothelial Cells and Neutrophils from Normal and Preeclamptic Pregnancies
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Chronic Hypoxia In Vivo Reduces Placental Oxidative Stress
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Trophoblast Apoptosis in Human Placenta at Term as Detected by Expression of a Cytokeratin 18 Degradation Product of Caspase
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High Altitude Residence During Pregnancy Alters Cytokine and Catecholamine Levels
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Maternal uterine artery Doppler studies at high altitude and sea level
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OXYGEN AND CARBON DIOXIDE CONTENT OF UMBILICAL ARTERY AND VEIN BLOOD IN TOXAEMIC AND NORMAL PREGNANCY*
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Vascular reactivity and electrolytes in normal and toxemic pregnancy
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Effects of Chronic Hypoxia on Maternal Vasodilation and Vascular Reactivity in Guinea Pig and Ovine Pregnancy
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On ‘oxygen and placental villous development: Origins of fetal hypoxia’
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Preeclampsia-A State of Sympathetic Overactivity
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Oxidative stress causes vascular dysfunction in the placenta
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Antigenic identification of cells in spiral artery trophoblastic invasion: Validation of histologic studies by triple-antibody immunocytochemistry
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Uterine blood flow in women at term
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Preeclampsia-Eclampsia Syndrome and Coagulation
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Increased Oxidative Stress in Pre-eclamptic Placenta is Associated with Altered Proteasome Activity and Protein Patterns
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PREGNANCY INDUCED HYPERTENSION
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Differential levels of T helper cytokines in preeclampsia, pregnancy, labor and puerperium
Omu, A. E., Al‐Qattan, F., Diejomaoh, M., & Al-Yatama, M. (1999) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1080/j.1600-0412.1999.780803.x · Cited by 20 · see citing works
Mechanisms Involved in Agonist-Induced Hyperaggregability of Platelets from Normal Pregnancy
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Correlation Between Umbilical Arterial Flow and Placental Morphology
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Anticholinergics Induce Eclamptic Seizures
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Measurement of uterine blood flow and uterine metabolism
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BLOOD FLOW OF THE GRAVID UTERUS*
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Increased biological oxidation and reduced anti-oxidant enzyme activity in pre-eclamptic placentae
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Endothelial Activation and Cell Adhesion Molecule Concentrations in Pregnant Women Living at High Altitude
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Are Maternal Diabetes and Preeclampsia Independent Simulators of Fetal Erythropoietin Production?
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Uteroplacental Blood Flow in Pregnancy Induced Hypertension
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Sympatho‐Adrenal Activity in Different Hypertensive Disorders in Pregnancy: A short review
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Sympathoadrenal and Cardiovascular Reactivity in Pregnancy-Induced Hypertension. II. Responses to Tilting
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Quantitative differences in arterial morphometry define the placental bed in preeclampsia
Salafia, C. M., Starzyk, K. A., Pezzullo, J. C., Lage, J. M., Parkash, V., Vercruysse, L., HANSSENS, M. C. A. J. A., & Pijnenborg, R. (1996) · Placenta · doi:10.1016/s0143-4004(96)90138-1 · Cited by 2 · see citing works
Mechanisms Involved in Agonist-Induced Hyperaggregability of Platelets from Normal Pregnancy
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Zamudio S.: High altitude and hypertension in pregnancy. In: Ed: F. Lyall. Cambridge University Press, Cambridge (2006)

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Pre-eclampsia
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DOI 10.1095/biolreprod.113.115592 Maternal and Fetoplacental Hypoxia Do Not Alter Circulating Angiogenic Growth
During, E., Pregnancy, H., Torricos, T., Al‐Khan, A., Alvarez, M., & Illsley, N. P. (2016)

Authors: Zamudio, S.
Affiliations: Rutgers New Jersey Medical School (US)
Corresponding author: Zamudio, Stacy
ORCID: Zamudio, Stacy
Venue: Frontiers in Bioscience
Publisher: IMR Press
Published: 2007
Volume: 12
Issue: 8-12
Pages: 2967
ISSN: 1093-4715 (ISSN-L)
1093-9946
DOI: 10.2741/2286
PMC: PMC6428070
OpenAlex: W2093270454
Cited by: 97
References: 127
Citations by year: 2026: 5 · 2025: 9 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 6 · 2012: 5
FWCI: 1.12
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Frontiers in bioscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: American Heart Association
National Institutes of Health
National Heart, Lung, and Blood Institute (HL-14985, P01HL014985)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD042737, HD 42737)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
Keywords: high-altitude hypoxia, preeclampsia, placental hypoxia, uteroplacental blood flow, oxidative stress, endothelial dysfunction, fetal growth restriction, pregnancy outcomes, placental development
MeSH terms: Altitude Sickness, Blood Circulation, Female, Humans, Placenta, Pre-Eclampsia, Pregnancy, Oxidative Stress

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