Trial reportPloS one2010
Effect of leucovorin (folinic acid) on the developmental quotient of children with Down's syndrome (trisomy 21) and influence of thyroid status.
Trial report in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 22 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
One-year Double-blind Placebo-controlled Phase 2-3 Study to Evaluate the Effect of Oral Folinic Acid Treatment (1mg/kg/d) on the Psychomotor Development of Young Down Syndrome Patients
Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children
Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Prenatal and Postnatal Therapies for Down's Syndrome and Associated Developmental Anomalies and Degenerative Deficits: A Systematic Review of Guidelines and Trials.Frontiers in medicine · 2022Pooled it
- Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome.Molecular medicine (Cambridge, Mass.) · 2020Pooled it
- Placebo Responses in Genetically Determined Intellectual Disability: A Meta-Analysis.PloS one · 2015Pooled it
- Thyroid hormone and folinic acid in young children with Down syndrome: the phase 3 ACTHYF trial.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Trial
- Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation.American journal of medical genetics. Part A · 2011Trial
- Integration of Metabolic Pathways and Micronutrient Signals Influences Neurodevelopment by Modulating Neural Stem Cell Dynamics.Molecular neurobiology · 2026Review
- Increased methylation levels of theEpigenomics · 2025Article
- Brain Mitochondrial Bioenergetics in Genetic Neurodevelopmental Disorders: Focus on Down, Rett and Fragile X Syndromes.International journal of molecular sciences · 2023Review
- Heterogeneous RNA editing and influence of ADAR2 on mesothelioma chemoresistance and the tumor microenvironment.Molecular oncology · 2022Article
- One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage.Frontiers in medicine · 2022Article
- Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis.Journal of personalized medicine · 2021Review
- Antioxidants in Down Syndrome: From Preclinical Studies to Clinical Trials.Antioxidants (Basel, Switzerland) · 2020Review
- Altered Folate Homeostasis in Children with Down Syndrome: A Potential Basis for Enhanced Methotrexate Toxicity.The Journal of pediatrics · 2020Article
- Challenges and Opportunities for Translation of Therapies to Improve Cognition in Down Syndrome.Trends in molecular medicine · 2020Article
- Genetic and epigenetic pathways in Down syndrome: Insights to the brain and immune system from humans and mouse models.Progress in brain research · 2020Review
- Trans-acting epigenetic effects of chromosomal aneuploidies: lessons from Down syndrome and mouse models.Epigenomics · 2017Review
- Changing Paradigms in Down Syndrome: The First International Conference of the Trisomy 21 Research Society.Molecular syndromology · 2016Article
- An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome.Scientific reports · 2016Article
- Trans effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models.Genome biology · 2015Article
- Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations.Drug design, development and therapy · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeven genes involved in folate metabolism are located on chromosome 21. Previous studies have shown that folate deficiency may contribute to mental retardation in Down's syndrome (DS). METHODOLOGY: We investigated the effect of oral folate supplementation (daily dose of 1.0+/-0.3 mg/kg) on cognitive functions in DS children, aged from 3 to 30 months. They received 1 mg/kg leucovorin or placebo daily, for 12 months, in a single-centre, randomised, double-blind study. Folinic acid (leucovorin, LV) was preferred to folic acid as its bioavailability is higher. The developmental age (DA) of the patients was assessed on the Brunet-Lezine scale, from baseline to the end of treatment.
resultsThe intent-to-treat analysis (113 patients) did not show a positive effect of leucovorin treatment. However, it identified important factors influencing treatment effect, such as age, sex, and concomitant treatments, including thyroid treatment in particular. A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period. This analysis of 87 patients (43 LV-treated vs. 44 patients on placebo) revealed a positive effect of leucovorin on developmental age (DA). DA was 53.1% the normal value with leucovorin and only 44.1% with placebo (p<0.05). This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment (59.5% vs. 41.8%, p<0.05). No adverse event related to leucovorin was observed.
conclusionThese results suggest that leucovorin improves the psychomotor development of children with Down's syndrome, at least in some subgroups of the DS population, particularly those on thyroxin treatment.
trial registrationClinicalTrials.gov, NCT00294593.
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What OpenQuestion holds
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.