Uterine artery blood flow, fetal hypoxia and fetal growth

Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

doi:10.1098/rstb.2014.0068

Cited by 127Pregnancy and preeclampsia studiesBirth, Development, and HealthHigh Altitude and Hypoxia

Uterine artery blood flow, fetal hypoxia and fetal growth

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Browne, Vaughn A., Julian, Colleen G., Toledo-Jaldin, Lillian, Cioffi-Ragan, Darleen, Vargas, Enrique, Moore, Lorna G.·2015·Philosophical Transactions of the Royal Society B: Biological Sciences

DOI 10.1098/rstb.2014.0068PMC PMC4305169

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Abstract

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success.

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In some studies of Andeans, absolute oxygen delivery to the gravid uterus at high altitude is maintained or even increased above lowland values despite low maternal pO2, while in others the uterine oxygen supply is less at high than low altitude irrespective of ancestry.
“Thus, in some studies of Andeans, absolute oxygen delivery to the gravid uterus at high altitude is maintained or even increased above lowland values, despite the low maternal pO2, while in others the uterine oxygen supply is less at high than low altitude irrespective of ancestry (69, 295, 443, 604).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [69]
In Andean women, the increase in uterine blood flow during pregnancy at high altitude can exceed that seen at low altitude.
“Indeed, in Andean women, the increase in uterine blood flow during pregnancy at high altitude can exceed that seen at low altitude (69, 295).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [69]
The dependence of placental steroid production on length of residency at altitude may explain some of the ethnic differences in birth weight seen between populations with long and short ancestry at altitude.
“In turn, this may explain some of the ethnic differences in birth weight seen between populations with long and short ancestry at altitude (69).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [69]

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Deep trophoblast invasion and spiral artery remodelling in the placental bed of the lowland gorilla
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“pr et er m (% ) 17 [7 ,3 7] (2 3) 5 [1 ,9 ]( 12 5) 19 [5 ,3 3] (2 9) , 0.”
Background
Comparative Morphometry of the Human Placenta at High Altitude and at Sea Level
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(2001) · doi:10.1002/1096-8644(200101)114:1
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Early Gestational Hypoxia and Adverse Developmental Outcomes
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Increased uterine artery blood flow in hypoxic murine pregnancy is not sufficient to prevent fetal growth restriction
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Vascular Disorders of Pregnancy Increase Susceptibility to Neonatal Pulmonary Hypertension in High-Altitude Populations.
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Pregnancy and newborn health - heat impacts and emerging solutions
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Mathematical modelling of the maternal cardiovascular system in the three stages of pregnancy
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Placental oxygen transfer reduces hypoxia-reoxygenation swings in fetal blood in a sheep model of gestational sleep apnea
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Luteolin-induced vasorelaxation in uterine arteries from normal pregnant rats
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Genomic Selection Signals in Andean Highlanders Reveal Adaptive Placental Metabolic Phenotypes That Are Disrupted in Preeclampsia
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Developmental programming of production and reproduction in dairy cows: III. Association of level of maternal milk production with offspring's birth weight, survival, productive and reproductive performance and AMH concentration from birth to the first lactation period
Harati, H. R. D., Mobedi, E., Allahyari, I., Gharagozlou, F., Vojgani, M., Baghbanani, R. H., Akbarinejad, A., & Akbarinejad, V. (2024) · Theriogenology · doi:10.1016/j.theriogenology.2024.01.001 · Cited by 13 · see citing works
Association between moderated level of air pollution and fetal growth: the potential role of noise exposure
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Why is human uterine artery blood flow during pregnancy so high?
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Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth
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Humans at high altitude: Hypoxia and fetal growth
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Chronic Hypoxia Diminishes Pregnancy-associated DNA Synthesis in Guinea Pig Uteroplacental Arteries
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Self-citation

Authors: Browne, V. A., Julian, C. G., Toledo-Jaldin, L., Cioffi-Ragan, D., Vargas, E., & Moore, L. G.
Affiliations: University of Colorado Denver (US)
Instituto Boliviano de Biología de Altura, La Paz, Bolivia
Department of Obstetrics and Gynecology, University of Colorado Denver, Aurora, CO 80045, USA
Corresponding author: Moore, Lorna G.
ORCID: Julian, Colleen G.
Vargas, Enrique
Moore, Lorna G.
Venue: Philosophical Transactions of the Royal Society B: Biological Sciences
Publisher: The Royal Society
Published: 2015-03-05
Volume: 370
Issue: 1663
Pages: 20140068
ISSN: 0962-8436 (ISSN-L)
1471-2970
DOI: 10.1098/rstb.2014.0068
PMC: PMC4305169
OpenAlex: W2166117052
Cited by: 127
References: 100
Citations by year: 2026: 2 · 2025: 7 · 2024: 16 · 2023: 17 · 2022: 13 · 2021: 17 · 2020: 12 · 2019: 14 · 2018: 12 · 2017: 8 · 2016: 2 · 2015: 7
FWCI: 10.97
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: royalsociety.org/journals/ethics-policies/data-sharing-mining/ (tdm)
Locations: Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders: U.S. Public Health Service (079647)
Fogarty International Center (TW 01188, R03TW001188)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD057022)
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 › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
Keywords: uterine artery blood flow, fetal hypoxia, fetal growth, fetal growth restriction, preeclampsia, gestational hypertension, high altitude, Andean women, Doppler ultrasound, fetal heart rate, evolutionary trade-offs, bipedalism, brain expansion, reproductive success
MeSH terms: Altitude, Biological Evolution, Female, Fetal Hypoxia, Fetus, Heart Rate, Humans, Models, Biological, Pregnancy, Regional Blood Flow, Fetal Development, Uterine Artery

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Uterine artery blood flow, fetal hypoxia and fetal growth

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