ArticleProceedings of the National Academy of Sciences of the United States of America1996
Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 3 of them syntheses 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
65 citing papers in PubMed, 3 syntheses or guidelines pooled it, 374 citations in OpenAlex.
- Quantitative assessment of maternal biomarkers related to one-carbon metabolism and neural tube defects.Scientific reports · 2015Pooled it
- Maternal reproductive history and the risk of congenital heart defects in offspring: a systematic review and meta-analysis.Pediatric cardiology · 2015Pooled it
- Pooled it
- Parental Genetic Variants, MTHFR 677C>T and MTRR 66A>G, Associated Differently with Fetal Congenital Heart Defect.BioMed research international · 2017Trial
- Single-cell mapping of homocysteine-induced perturbations in avian embryogenesis using LMO and BD rhapsody transcriptomics.iScience · 2026Article
- Maternal Dietary B-Complex Vitamin Pattern and Risk of Complex Congenital Heart Defects in a Mexican Population.Nutrients · 2026Article
- Prevalence and Metabolic Characterization of Polycystic Ovary Syndrome in a Cohort of Patients Diagnosed with Spina Bifida: Study Protocol.Children (Basel, Switzerland) · 2025Article
- Maternal micronutrient biomarkers and risk of non-syndromic cleft lip/palate: A case-control study.Oral diseases · 2025Article
- Effects of Gender Differences inInternational journal of genomics · 2025Article
- Article
- Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease.Nutrients · 2023Article
- Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease.Cell reports. Medicine · 2023Article
- Article
- Profiling the Influence of Gene Variants Related to Folate-Mediated One-Carbon Metabolism on the Outcome of In Vitro Fertilization (IVF) with Donor Oocytes in Recipients Receiving Folic Acid Fortification.International journal of molecular sciences · 2022Article
- Homocysteine-Thiolactone Modulates Gating of Mitochondrial Voltage-Dependent Anion Channel (VDAC) and Protects It from Induced Oxidative Stress.The Journal of membrane biology · 2022Article
- Homocysteine-induced neural tube defects in chick embryos via oxidative stress and DNA methylation associated transcriptional down-regulation of miR-124.Toxicology research · 2021Article
- Distribution of Methionine Synthase Reductase (MTRR) Gene A66G Polymorphism in Indian Population.Indian journal of clinical biochemistry : IJCB · 2021Article
- Epigenetic Regulation of Cardiac Neural Crest Cells.Frontiers in cell and developmental biology · 2021Review
- Risk factors for transposition of the great arteries in Saudi population.Saudi medical journal · 2020Article
- Peripheral neuropathy in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The biological basis or mechanism whereby folate supplementation protects against heart and neural tube defect is unknown. It has been hypothesized that the amino acid homocysteine may be the teratogenic agent, since serum homocysteine increases in folate depletion; however, this hypothesis has not been tested. In this study, avian embryos were treated directly with D,L-homocysteine or with L-homocysteine thiolactone, and a dose response was established. Of embryos treated with 50 microliters of the teratogenic dose (200 mM D,L-homocysteine or 100 mM L-homocysteine thiolactone) on incubation days 0, 1, and 2 and harvested at 53 h (stage 14), 27% showed neural tube defects. To determine the effect of the teratogenic dose on the process of heart septation, embryos were treated during incubation days 2, 3, and 4; then they were harvested at day 9 following the completion of septation. Of surviving embryos, 23% showed ventricular septal defects, and 11% showed neural tube defects. A high percentage of the day 9 embryos also showed a ventral closure defect. The teratogenic dose was shown to raise serum homocysteine to over 150 nmol/ml, compared with a normal level of about 10 nmol/ml. Folate supplementation kept the rise in serum homocysteine to approximately 45 nmol/ml, and prevented the teratogenic effect. These results support the hypothesis that homocysteine per se causes dysmorphogenesis of the heart and neural tube, as well as of the ventral wall.
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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.