title: Periconceptional Folic Acid Supplementation and Infant Risk of Congenital Heart Defects in Norway 1999-2009.
abstract: BACKGROUND
  The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs.
  
  
  METHODS
  Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999-2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression.
  
  
  RESULTS
  Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30].
  
  
  CONCLUSIONS
  Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation.
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Elisabeth
authors.identifier: http://orcid.org/0000-0002-4988-1203
authors.initials: E
authors.lastname: Leirgul
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Trude
authors.initials: T
authors.lastname: Gildestad
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.|Department of Clinical Research, Haukeland University Hospital, Bergen, Norway.
authors.forename: Roy Miodini
authors.initials: RM
authors.lastname: Nilsen
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Fomina
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Brodwall
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Greve
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.|Norwegian Institute of Public Health, Bergen, Norway.
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.affiliation: Department of Pediatrics, Oslo University Hospital, Oslo, Norway.
authors.forename: Henrik
authors.initials: H
authors.lastname: Holmstrøm
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.|Norwegian Institute of Public Health, Bergen, Norway.
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Øyen
mesh_terms: D000328:Adult; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006330:Heart Defects, Congenital / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009664:Norway / Q000453:epidemiology; D016742:Preconception Care; D011247:Pregnancy; D037841:Pregnant People; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D013997:Time Factors
chemical_list: D005492:Folic Acid
keywords: Norway; cohort study; congenital heart defects; epidemiology; folic acid supplementation