ArticleCirculation2016
Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes.
Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03725878 (Effectiveness of Comprehensive Tertiary Interventions on Incidence and Clinical Outcomes of Birth Defects), which is not on this map. Cited by 78 papers, 2 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.
Effectiveness of Comprehensive Tertiary Interventions on Incidence and Clinical Outcomes of Birth Defects : a Cluster Randomisation Intervention Trial
Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Association of MTHFD1 G1958A (rs2236225) gene polymorphism with the risk of congenital heart disease: a systematic review and meta-analysis.BMC medical genomics · 2025Pooled it
- Evaluation of the association between maternal folic acid supplementation and the risk of congenital heart disease: a systematic review and meta-analysis.Nutrition journal · 2022Pooled it
- Association between maternal MTHFR and MTRR gene polymorphisms and the risk of congenital heart disease in newborns.BMC pediatrics · 2026Article
- Cardiovascular Risk in Adolescents with Congenital Heart Disease Living in a Low-Income Region: Cross-Sectional Associations with Clinical, Behavioral and Sociodemographic Factors.Pediatric cardiology · 2026Article
- Congenital heart disease and folate pathway gene polymorphisms: findings from a North Indian cohort.BMC cardiovascular disorders · 2026Article
- Trends in Congenital Heart Disease Hospitalizations: What Nearly 50 Years of Longitudinal Data and Segmented Regression Reveal.Journal of the American Heart Association · 2026Article
- Trends and Prevalence of Modifiable Risk Factors for Birth Defects Among U.S. Women of Reproductive Age: National Health and Nutrition Examination Survey 2007 to March 2020.American journal of preventive medicine · 2025Article
- Cost-effectiveness of nirsevimab and maternal RSVpreF for preventing respiratory syncytial virus disease in infants across Canada.BMC medicine · 2025Article
- Efficacy of tea as an ideal vehicle for therapeutic vitamin replacement in women with low folate and vitamin B12 status in Assam: a placebo-controlled interventional clinical trial.BMJ nutrition, prevention & health · 2025Article
- Maternal multivitamin supplementation mitigates the risk of fetal congenital heart disease associated with high indoor total volatile organic compounds exposure in east china: a case-control study.Environmental health : a global access science source · 2024Article
- Risk of venous thromboembolism in patients with congenital heart disease: a nationwide, register-based, case-control study.European heart journal open · 2024Article
- Maternal Serum Folate During Pregnancy and Congenital Heart Disease in Offspring.JAMA network open · 2024Article
- Ischemic Stroke in Patients With Congenital Heart Disease and Atrial Fibrillation.Journal of the American Heart Association · 2024Article
- Article
- Human Genetics of Congenital Heart Defects.Advances in experimental medicine and biology · 2024Review
- Cost-effectiveness analysis of nirsevimab and maternal RSVpreF vaccine strategies for prevention of Respiratory Syncytial Virus disease among infants in Canada: a simulation study.Lancet regional health. Americas · 2023Article
- Analysis of Gut Characteristics and Microbiota Changes with Maternal Supplementation in a Neural Tube Defect Mouse Model.Nutrients · 2023Article
- Relationships between Maternal Folic Acid Supplementation andNutrients · 2023Article
- Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease.Nutrients · 2023Article
- Association of maternal depression and hypothyroidism with infant gastroschisis: a population-based cohort study in Canada.Scientific reports · 2023Article
18 more citing papers are in PubMed but not listed here.
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12 authors.
Funding
Abstract
backgroundPrevious studies have yielded inconsistent results for the effects of periconceptional multivitamins containing folic acid and of folic acid food fortification on congenital heart defects (CHDs).
methodsWe carried out a population-based cohort study (N=5 901 701) of all live births and stillbirths (including late-pregnancy terminations) delivered at ≥20 weeks' gestation in Canada (except Québec and Manitoba) from 1990 to 2011. CHD cases were diagnosed at birth and in infancy (n=72 591). We compared prevalence rates and temporal trends in CHD subtypes before and after 1998 (the year that fortification was mandated). An ecological study based on 22 calendar years, 14 geographic areas, and Poisson regression analysis was used to quantify the effect of folic acid food fortification on nonchromosomal CHD subtypes (n=66 980) after controlling for changes in maternal age, prepregnancy diabetes mellitus, preterm preeclampsia, multiple birth, and termination of pregnancy.
resultsThe overall birth prevalence rate of CHDs was 12.3 per 1000 total births. Rates of most CHD subtypes decreased between 1990 and 2011 except for atrial septal defects, which increased significantly. Folic acid food fortification was associated with lower rates of conotruncal defects (adjusted rate ratio [aRR], 0.73, 95% confidence interval [CI], 0.62-0.85), coarctation of the aorta (aRR, 0.77; 95% CI, 0.61-0.96), ventricular septal defects (aRR, 0.85; 95% CI, 0.75-0.96), and atrial septal defects (aRR, 0.82; 95% CI, 0.69-0.95) but not severe nonconotruncal heart defects (aRR, 0.81; 95% CI, 0.65-1.03) and other heart or circulatory system abnormalities (aRR, 0.98; 95% CI, 0.89-1.11).
conclusionsThe association between food fortification with folic acid and a reduction in the birth prevalence of specific CHDs provides modest evidence for additional benefit from this intervention.
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