Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes

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Abstract

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Abstract

Background:

Previous 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).

Methods:

We 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.

Results:

The 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).

ConclusionS:

The 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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Most cited references 36

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Permutation tests for joinpoint regression with applications to cancer rates.

H. Kim, M P Fay, E. J. Feuer … (2000)

The identification of changes in the recent trend is an important issue in the analysis of cancer mortality and incidence data. We apply a joinpoint regression model to describe such continuous changes and use the grid-search method to fit the regression function with unknown joinpoints assuming constant variance and uncorrelated errors. We find the number of significant joinpoints by performing several permutation tests, each of which has a correct significance level asymptotically. Each p-value is found using Monte Carlo methods, and the overall asymptotic significance level is maintained through a Bonferroni correction. These tests are extended to the situation with non-constant variance to handle rates with Poisson variation and possibly autocorrelated errors. The performance of these tests are studied via simulations and the tests are applied to U.S. prostate cancer incidence and mortality rates. Copyright 2000 John Wiley & Sons, Ltd.

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The incidence of congenital heart disease.

Julien Hoffman, Samuel Kaplan (2002)

This study was designed to determine the reasons for the variability of the incidence of congenital heart disease (CHD), estimate its true value and provide data about the incidence of specific major forms of CHD. The incidence of CHD in different studies varies from about 4/1,000 to 50/1,000 live births. The relative frequency of different major forms of CHD also differs greatly from study to study. In addition, another 20/1,000 live births have bicuspid aortic valves, isolated anomalous lobar pulmonary veins or a silent patent ductus arteriosus. The incidences reported in 62 studies published after 1955 were examined. Attention was paid to the ways in which the studies were conducted, with special reference to the increased use of echocardiography in the neonatal nursery. The total incidence of CHD was related to the relative frequency of ventricular septal defects (VSDs), the most common type of CHD. The incidences of individual major forms of CHD were determined from 44 studies. The incidence of CHD depends primarily on the number of small VSDs included in the series, and this number in turn depends upon how early the diagnosis is made. If major forms of CHD are stratified into trivial, moderate and severe categories, the variation in incidence depends mainly on the number of trivial lesions included. The incidence of moderate and severe forms of CHD is about 6/1,000 live births (19/1,000 live births if the potentially serious bicuspid aortic valve is included), and of all forms increases to 75/1,000 live births if tiny muscular VSDs present at birth and other trivial lesions are included. Given the causes of variation, there is no evidence for differences in incidence in different countries or times.

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Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics.

Mary Pierpont, Craig Basson, D Woodrow Benson … (2007)

The intent of this review is to provide the clinician with a summary of what is currently known about the contribution of genetics to the origin of congenital heart disease. Techniques are discussed to evaluate children with heart disease for genetic alterations. Many of these techniques are now available on a clinical basis. Information on the genetic and clinical evaluation of children with cardiac disease is presented, and several tables have been constructed to aid the clinician in the assessment of children with different types of heart disease. Genetic algorithms for cardiac defects have been constructed and are available in an appendix. It is anticipated that this summary will update a wide range of medical personnel, including pediatric cardiologists and pediatricians, adult cardiologists, internists, obstetricians, nurses, and thoracic surgeons, about the genetic aspects of congenital heart disease and will encourage an interdisciplinary approach to the child and adult with congenital heart disease.

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Author and article information

Journal

Journal ID (nlm-ta): Circulation

Journal ID (iso-abbrev): Circulation

Journal ID (publisher-id): CIR

Title: Circulation

Publisher: Lippincott Williams & Wilkins

ISSN (Print): 0009-7322

ISSN (Electronic): 1524-4539

Publication date (Print): 30 August 2016

Publication date (Electronic): 29 August 2016

Volume: 134

Issue: 9

Pages: 647-655

Affiliations

From Maternal, Child and Youth Health, Surveillance and Epidemiology Division, Centre for Chronic Disease Prevention, Public Health Agency of Canada, Ottawa, ON, Canada (S. Liu, W.L., J.A.L.); Department of Obstetrics and Gynaecology, University of British Columbia and the Children’s and Women’s Hospital of British Columbia, Vancouver, BC, Canada (K.S.J., S. Lisonkova, K.L.); School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada (K.S.J.); Department of Obstetrics and Gynaecology, Dalhousie University, NS, Canada (M.V.d.H.); Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada (J.E.); School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada (J.L.); Departments of Pediatrics and Community Health Sciences, University of Calgary, Calgary, AB, Canada (R.S.); and Departments of Pediatrics and Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada (M.S.K.).

Author notes

Correspondence to: Shiliang Liu, MD, PhD, Surveillance and Epidemiology Division, CCDPC-Public Health Agency of Canada, 785 Carling Ave, AL 6804A Ottawa, ON, Canada K1A 0K9. E-mail shiliang.liu@ 123456phac-aspc.gc.ca

Article

Accession ID: 00005

DOI: 10.1161/CIRCULATIONAHA.116.022126

PMC ID: 4998126

PubMed ID: 27572879

SO-VID: 76f70b03-ffc3-4a1a-865c-2f2fb0d62b8a

License:

Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

History

Date received : 17 February 2016

Date accepted : 27 June 2016

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Keywords: association,folic acid,heart defects, congenital,primary prevention

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Keywords: association, folic acid, heart defects, congenital, primary prevention

Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes

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Most cited references 36

Permutation tests for joinpoint regression with applications to cancer rates.

The incidence of congenital heart disease.

Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics.

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