title: Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors: 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.). shiliang.liu@phac-aspc.gc.ca.
authors: Shiliang
authors: S
authors: Liu
authors: 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.).
authors: K S
authors: KS
authors: Joseph
authors: 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.).
authors: Wei
authors: W
authors: Luo
authors: 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.).
authors: Juan Andrés
authors: JA
authors: León
authors: 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.).
authors: Sarka
authors: S
authors: Lisonkova
authors: 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.).
authors: Michiel
authors: M
authors: Van den Hof
authors: 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.).
authors: Jane
authors: J
authors: Evans
authors: 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.).
authors: Ken
authors: K
authors: Lim
authors: 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.).
authors: Julian
authors: J
authors: Little
authors: 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.).
authors: Reg
authors: R
authors: Sauve
authors: 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.).
authors: Michael S
authors: MS
authors: Kramer
mesh_terms: D000328:Adult; D001723:Birth Rate / Q000639:trends; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005527:Food, Fortified; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011159:Population Surveillance; D011247:Pregnancy; D016896:Treatment Outcome
chemical_list: D005492:Folic Acid
keywords: association; folic acid; heart defects, congenital; primary prevention