ArticleProceedings of the National Academy of Sciences of the United States of America2015
Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06807255 (Lactate Values During Labour and Their Correlation With Maternal and Foetal Outcome), which is not on this map. Cited by 27 papers.
What it found
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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.
Lactate Values During Labour and Their Correlation With Maternal and Foetal Outcome: a Prospective Observational Single-centre Study
Who cites it
27 citing papers in PubMed, 60 citations in OpenAlex.
- Maternal anaemia and the risk of postpartum haemorrhage: a cohort analysis of data from the WOMAN-2 trial.The Lancet. Global health · 2023Trial
- Energy substrate preference and metabolic flexibility in quiescent and oxytocin-stimulated human myometrial cells.iScience · 2026Article
- Case-specific optimal extracorporeal membrane oxygenation configuration for cardiogenic shock in the peripartum period: a case report.Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs · 2026Article
- Metabolic Flexibility and Energy Substrate Utilization Regulate Contractility in the Human Myometrium.bioRxiv : the preprint server for biology · 2026Article
- Regulatory T cells in human pregnancy: mechanisms, dysregulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Lactate values during labour and their correlation with maternal and fetal outcome.Reproduction & fertility · 2026Article
- HIF1A facilitates hypoxia-induced changes in H3K27ac modification to promote myometrial contractility.Communications biology · 2025Article
- Voltage-Gated Calcium Channels and the Parity-Dependent Differential Uterine Response to Oxytocin in Rats.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Assessment of Tissue Expression of the Oxytocin-Vasopressin Pathway in the Placenta of Women with a First-Episode Psychosis during Pregnancy.International journal of molecular sciences · 2023Article
- Golgi Reassembly Stacking Protein 2 Modulates Myometrial Contractility during Labor by Affecting ATP Production.International journal of molecular sciences · 2023Article
- HIF-1α is essential for the augmentation of myometrial contractility during labor†.Biology of reproduction · 2022Article
- Cardiac output-guided maternal position therapy for preterm labor-it's time for a trial.Acta obstetricia et gynecologica Scandinavica · 2022Article
- Ferroptosis and Its Emerging Role in Pre-Eclampsia.Antioxidants (Basel, Switzerland) · 2022Review
- Ferroptosis induces membrane blebbing in placental trophoblasts.Journal of cell science · 2022Article
- Parity associates with chromosomal damage in uterine leiomyomas.Nature communications · 2021Article
- Review
- Calcium-Activated Chloride Channels in Myometrial and Vascular Smooth Muscle.Frontiers in physiology · 2021Review
- Integrated Proteotranscriptomics of Human Myometrium in Labor Landscape Reveals the Increased Molecular Associated With Inflammation Under Hypoxia Stress.Frontiers in immunology · 2021Article
- PLA2G6 guards placental trophoblasts against ferroptotic injury.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Activation of Autophagy in Human Uterine Myometrium During Labor.Reproductive sciences (Thousand Oaks, Calif.) · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For successful birth, contractions need to become progressively stronger. The underlying mechanisms are unknown, however. We have found that a novel mechanism, hypoxia-induced force increase (HIFI), is switched on selectively, at term, and is essential to strengthening contractions. HIFI is initiated as contractions cyclically reduce blood flow and produce repeated hypoxic stresses, with associated metabolic and transcriptomic changes. The increases in contractility are a long-lasting, oxytocin-independent, intrinsic mechanism present only in the full-term pregnant uterus. HIFI is inhibited by adenosine receptor antagonism and blockade of cyclooxygenase-2 signaling, and partially reproduced by brief episodes of acidic (but not alkalotic) pH. HIFI explains how labor can progress despite paradoxical metabolic challenge, and provides a new mechanistic target for the 1 in 10 women suffering dysfunctional labor because of poor contractions.
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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.