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

Shiliang Liu, K S Joseph, Wei Luo, Juan Andrés León, Sarka Lisonkova, Michiel Van den Hof, Jane Evans, Ken Lim, Julian Little, Reg Sauve, Michael S Kramer, Canadian Perinatal Surveillance System (Public Health Agency of Canada), Shiliang Liu, K S Joseph, Wei Luo, Juan Andrés León, Sarka Lisonkova, Michiel Van den Hof, Jane Evans, Ken Lim, Julian Little, Reg Sauve, Michael S Kramer, Canadian Perinatal Surveillance System (Public Health Agency of Canada)

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.

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

© 2016 The Authors.

Figures

Figure.
Figure.
Temporal trends in congenital heart defects (CHDs) by subtype, Canada (excluding Québec and Manitoba), 1990 to 2011. Left y axis, conotruncal defects, coarctation of aorta, and nonconotruncal defects. Right y axis, ventricular septal defect (VSD), atrial septal defect (ASD), and other heart and circulatory anomalies.

References

    1. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39:1890–1900.
    1. Dolk H, Loane M, Garne E European Surveillance of Congenital Anomalies (EUROCAT) Working Group. Congenital heart defects in Europe: prevalence and perinatal mortality, 2000 to 2005. Circulation. 2011;123:841–849. doi: 10.1161/CIRCULATIONAHA.110.958405.
    1. Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005. J Pediatr. 2008;153:807–813. doi: 10.1016/j.jpeds.2008.05.059.
    1. Oyen N, Poulsen G, Boyd HA, Wohlfahrt J, Jensen PK, Melbye M. National time trends in congenital heart defects, Denmark, 1977-2005. Am Heart J. 2009;157:467–473.e1. doi: 10.1016/j.ahj.2008.10.017.
    1. Public Health Agency of Canada. Congenital anomalies in Canada 2013: a perinatal health surveillance report. . Accessed October 6, 2015.
    1. Botto LD, Lin AE, Riehle-Colarusso T, Malik S, Correa A National Birth Defects Prevention Study. Seeking causes: classifying and evaluating congenital heart defects in etiologic studies. Birth Defects Res A Clin Mol Teratol. 2007;79:714–727. doi: 10.1002/bdra.20403.
    1. Jenkins KJ, Correa A, Feinstein JA, Botto L, Britt AE, Daniels SR, Elixson M, Warnes CA, Webb CL American Heart Association Council on Cardiovascular Disease in the Young. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007;115:2995–3014. doi: 10.1161/CIRCULATIONAHA.106.183216.
    1. Liu S, Joseph KS, Lisonkova S, Rouleau J, Van den Hof M, Sauve R, Kramer MS Canadian Perinatal Surveillance System (Public Health Agency of Canada) Association between maternal chronic conditions and congenital heart defects: a population-based cohort study. Circulation. 2013;128:583–589. doi: 10.1161/CIRCULATIONAHA.112.001054.
    1. Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327:1832–1835. doi: 10.1056/NEJM199212243272602.
    1. Czeizel AE. Periconceptional folic acid containing multivitamin supplementation. Eur J Obstet Gynecol Reprod Biol. 1998;78:151–161.
    1. Czeizel AE. The primary prevention of birth defects: multivitamins or folic acid? Int J Med Sci. 2004;1:50–61.
    1. Huhta JC, Linask K, Bailey L. Recent advances in the prevention of congenital heart disease. Curr Opin Pediatr. 2006;18:484–489. doi: 10.1097/01.mop.0000245347.45336.d7.
    1. Bailey LB, Berry RJ. Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage. Am J Clin Nutr. 2005;81(suppl):1213S–1217S.
    1. Botto LD, Olney RS, Erickson JD. Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am J Med Genet C Semin Med Genet. 2004;125C:12–21. doi: 10.1002/ajmg.c.30004.
    1. Czeizel AE, Dudás I, Vereczkey A, Bánhidy F. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects. Nutrients. 2013;5:4760–4775. doi: 10.3390/nu5114760.
    1. Shaw GM, Carmichael SL, Yang W, Lammer EJ. Periconceptional nutrient intakes and risks of conotruncal heart defects. Birth Defects Res A Clin Mol Teratol. 2010;88:144–151. doi: 10.1002/bdra.20648.
    1. Scanlon KS, Ferencz C, Loffredo CA, Wilson PD, Correa-Villaseñor A, Khoury MJ, Willett WC. Preconceptional folate intake and malformations of the cardiac outflow tract: Baltimore-Washington Infant Study Group. Epidemiology. 1998;9:95–98.
    1. Ionescu-Ittu R, Marelli AJ, Mackie AS, Pilote L. Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada. BMJ. 2009;338:b1673.
    1. Robbins JM, Tilford JM, Bird TM, Cleves MA, Reading JA, Hobbs CA. Hospitalizations of newborns with folate-sensitive birth defects before and after fortification of foods with folic acid. Pediatrics. 2006;118:906–915. doi: 10.1542/peds.2005-2784.
    1. van Beynum IM, Kapusta L, Bakker MK, den Heijer M, Blom HJ, de Walle HE. Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: a registry-based case-control study in the northern Netherlands. Eur Heart J. 2010;31:464–471. doi: 10.1093/eurheartj/ehp479.
    1. Khoshnood B, Loane M, Garne E, Addor MC, Arriola L, Bakker M, Barisic I, Bianca S, Boyd P, Calzolari E, Doray B, Draper E, Gatt M, Haeusler M, Melve KK, Latos-Bielenska A, McDonnell B, Mullaney C, Nelen V, O’Mahony M, Pierini A, Queisser-Luft A, Randrianaivo H, Rankin J, Rissmann A, Salvador J, Tucker D, Verellen-Dumoulin C, Wellesley D, Zymak-Zakutnya N, Dolk H. Recent decrease in the prevalence of congenital heart defects in Europe. J Pediatr. 2013;162:108–13.e2. doi: 10.1016/j.jpeds.2012.06.035.
    1. Leirgul E, Gildestad T, Nilsen RM, Fomina T, Brodwall K, Greve G, Vollset SE, Holmstrøm H, Tell GS, Øyen N. Periconceptional folic acid supplementation and infant risk of congenital heart defects in Norway 1999–2009. Paediatr Perinat Epidemiol. 2015;29:391–400. doi: 10.1111/ppe.12212.
    1. Czeizel AE, Vereczkey A, Szabó I. Folic acid in pregnant women associated with reduced prevalence of severe congenital heart defects in their children: a national population-based case-control study. Eur J Obstet Gynecol Reprod Biol. 2015;193:34–39. doi: 10.1016/j.ejogrb.2015.06.024.
    1. De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B, Evans JA, Van den Hof MC, Zimmer P, Crowley M, Fernandez B, Lee NS, Niyonsenga T. Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med. 2007;357:135–142. doi: 10.1056/NEJMoa067103.
    1. Liu S, West R, Randell E, Longerich L, O’connor KS, Scott H, Crowley M, Lam A, Prabhakaran V, McCourt C. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects. BMC Pregnancy Childbirth. 2004;4:20. doi: 10.1186/1471-2393-4-20.
    1. Liu S, Joseph KS, Kramer MS, Allen AC, Sauve R, Rusen ID, Wen SW Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. Relationship of prenatal diagnosis and pregnancy termination to overall infant mortality in Canada. JAMA. 2002;287:1561–1567.
    1. Joseph KS, Kinniburgh B, Hutcheon JA, Mehrabadi A, Basso M, Davies C, Lee L. Determinants of increases in stillbirth rates from 2000 to 2010. CMAJ. 2013;185:E345–E351. doi: 10.1503/cmaj.121372.
    1. Auger N, Fraser WD, Healy-Profitós J, Arbour L. Association between preeclampsia and congenital heart defects. JAMA. 2015;314:1588–1598. doi: 10.1001/jama.2015.12505.
    1. Brodwall K, Leirgul E, Greve G, Vollset SE, Holmstrøm H, Tell GS, Øyen N. Possible common aetiology behind maternal preeclampsia and congenital heart defects in the child: a Cardiovascular Diseases in Norway Project Study. Paediatr Perinat Epidemiol. 2016;30:76–85. doi: 10.1111/ppe.12252.
    1. Public Health Agency of Canada. Canadian Perinatal Health Report, 2008 Edition. 2008. . Accessed June 8, 2016.
    1. Joseph KS, Fahey J Canadian Perinatal Surveillance System. Validation of perinatal data in the Discharge Abstract Database of the Canadian Institute for Health Information. Chronic Dis Can. 2009;29:96–100.
    1. Ray GJ. Folic acid food fortification in Canada. Nutr Res. 2004;62(pt 2):S35–S39.
    1. Pierpont ME, Basson CT, Benson DW, Jr, Gelb BD, Giglia TM, Goldmuntz E, McGee G, Sable CA, Srivastava D, Webb CL American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young. 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. Circulation. 2007;115:3015–3038. doi: 10.1161/CIRCULATIONAHA.106.183056.
    1. Kuhn L, Davidson LL, Durkin MS. Use of Poisson regression and time series analysis for detecting changes over time in rates of child injury following a prevention program. Am J Epidemiol. 1994;140:943–955.
    1. Esteve J, Benhamous E, Raymond L. In: Statistical Methods in Cancer Research Volume 4, Descriptive Epidemiology. Lyon, France: IARC; 1994. Space-time variations and group correlations. IARC Sci Publ 128.
    1. Liu S, Joseph KS, Wen SW. Trends in fetal and infant deaths caused by congenital anomalies. Semin Perinatol. 2002;26:268–276.
    1. Liu S, Joseph KS, Wen SW, Kramer MS, Marcoux S, Ohlsson A, Sauve R Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. Secular trends in congenital anomaly-related fetal and infant mortality in Canada, 1985-1996. Am J Med Genet. 2001;104:7–13.
    1. Yazdy MM, Honein MA, Xing J. Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply. Birth Defects Res A Clin Mol Teratol. 2007;79:16–23. doi: 10.1002/bdra.20319.
    1. Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for Joinpoint regression with applications to cancer rates. Stat Med. 2000;19:335–351.
    1. National Cancer Institute, Department of Cancer Control and Population Sciences. Joinpoint trend analysis software. . Accessed June 8, 2016.
    1. Turner LA, McCourt C. Folic acid fortification: what does it mean for patients and physicians? CMAJ. 1998;158:773–776.
    1. Ray JG. Efficacy of Canadian folic acid food fortification. Food Nutr Bull. 2008;29(suppl):S225–S230.
    1. Herskind AM, Almind Pedersen D, Christensen K. Increased prevalence of congenital heart defects in monozygotic and dizygotic twins. Circulation. 2013;128:1182–1188. doi: 10.1161/CIRCULATIONAHA.113.002453.
    1. Wang W, Wang Y, Gong F, Zhu W, Fu S. MTHFR C677T polymorphism and risk of congenital heart defects: evidence from 29 case-control and TDT studies. PLoS One. 2013;8:e58041. Doi: 10.1371/journal.pone.0058041.
    1. Padmanabhan N, Jia D, Geary-Joo C, Wu X, Ferguson-Smith AC, Fung E, Bieda MC, Snyder FF, Gravel RA, Cross JC, Watson ED. Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development. Cell. 2013;155:81–93.
    1. Brown HK, Wilk P. Changes in smoking during pregnancy in Ontario, 1995 to 2010: results from the Canadian community health survey. J Obstet Gynaecol Can. 2014;36:878–884.

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