ArticlePLoS biology2019
Intervention against hypertension in the next generation programmed by developmental hypoxia.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Guidelines for assessing maternal cardiovascular physiology during pregnancy and postpartum.American journal of physiology. Heart and circulatory physiology · 2024Guideline
- Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals.BioMed research international · 2022Trial
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Insights from animal models: Dissecting the independent roles of oxygen and nutrients in the fetal origins of cardiovascular disease.The Journal of physiology · 2026Review
- Brain sparing in fetal growth restriction: The double-edged sword of fetal hypoxaemia.The Journal of physiology · 2026Review
- Cardiovascular Consequences of Late-Gestational Hypoxia in Adult Female Rat Offspring and the Effects of Maternal Ergothioneine Treatment.Physiological research · 2026Article
- Maternal cardiometabolic dysfunction and fetal sex-specific alterations to uterine vascular reactivity in an ovine model of obesity during pregnancy.The Journal of physiology · 2026Article
- Conserved gene expression patterns in the placenta underlie pregnancy complications associated with hypoxia in mice and humans.Cellular and molecular life sciences : CMLS · 2026Article
- Redox-Driven Precision Medicine for Life-Course Prevention of Cardiovascular-Kidney-Metabolic Syndrome.Antioxidants (Basel, Switzerland) · 2026Review
- In vivo and ex vivo cardiovascular haemodynamic responses of preterm growth-restricted lambs to perinatal asphyxia.Clinical science (London, England : 1979) · 2025Article
- Cocoa shell extract supplementation in hypertensive rats induces outward hypertrophic remodelling in mesenteric resistance arteries, reducing fibrosis.Experimental physiology · 2025Article
- Compromised cardiopulmonary transition in fetal growth restricted and small for gestational age neonates.The Journal of physiology · 2025Review
- Translatable in-vivo investigation of effects of progressive hypoxia in pregnancy on fetal cardiac structure and function in sheep.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2025Article
- Antioxidants: powering the fight against fetal hypoxia.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Effects of a postnatal high-salt diet on cardiac function in offspring from hypoxic pregnancies.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- Fetal growth and congenital heart disease at high altitude.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Fetal programming under maternal heat stress: a focus on skeletal muscle growth and nutrition in livestock.Journal of developmental origins of health and disease · 2025Review
- Antenatal Vitamin C differentially affects lung development in normally grown and growth restricted sheep.Pediatric research · 2025Article
- Hypoxic pregnancy promotes fibrosis and increases stress metabolites in the ovine fetal liver.The Journal of physiology · 2025Article
- Maternal MitoQ Treatment Is Protective Against Programmed Alterations in CYP Activity Due to Antenatal Dexamethasone.Pharmaceutics · 2025Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy and increased cardiovascular disease in the adult offspring. However, translational studies isolating mechanisms to design intervention are lacking. Sheep and humans share similar precocial developmental milestones in cardiovascular anatomy and physiology. We tested the hypothesis in sheep that maternal treatment with antioxidants protects against fetal growth restriction and programmed hypertension in adulthood in gestation complicated by chronic fetal hypoxia, the most common adverse consequence in human pregnancy. Using bespoke isobaric chambers, chronically catheterized sheep carrying singletons underwent normoxia or hypoxia (10% oxygen [O2]) ± vitamin C treatment (maternal 200 mg.kg-1 IV daily) for the last third of gestation. In one cohort, the maternal arterial blood gas status, the value at which 50% of the maternal hemoglobin is saturated with oxygen (P50), nitric oxide (NO) bioavailability, oxidative stress, and antioxidant capacity were determined. In another, naturally delivered offspring were raised under normoxia until early adulthood (9 months). Lambs were chronically instrumented and cardiovascular function tested in vivo. Following euthanasia, femoral arterial segments were isolated and endothelial function determined by wire myography. Hypoxic pregnancy induced fetal growth restriction and fetal oxidative stress. At adulthood, it programmed hypertension by enhancing vasoconstrictor reactivity and impairing NO-independent endothelial function. Maternal vitamin C in hypoxic pregnancy improved transplacental oxygenation and enhanced fetal antioxidant capacity while increasing NO bioavailability, offsetting constrictor hyper-reactivity and replenishing endothelial function in the adult offspring. These discoveries provide novel insight into mechanisms and interventions against fetal growth restriction and adult-onset programmed hypertension in an animal model of complicated pregnancy in a species of similar temporal developmental milestones to humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.