Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway

Nina Øyen; Sjurdur F. Olsen; Saima Basit; Elisabeth Leirgul; Marin Strøm; Lisbeth Carstensen; Charlotta Granström; Grethe S. Tell; Per Magnus; Stein E. Vollset; Jan Wohlfahrt; Mads Melbye

doi:10.1161/JAHA.118.011615

Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway

Nina Øyen^*, Sjurdur F. Olsen, Saima Basit, Elisabeth Leirgul, Marin Strøm, Lisbeth Carstensen, Charlotta Granström, Grethe S. Tell, Per Magnus, Stein E. Vollset, Jan Wohlfahrt, Mads Melbye

^*Corresponding author for this work

Department of Clinical Medicine

13 Citations (Scopus)

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Abstract

Background: Evidence linking individual-level maternal folic acid supplementation to offspring risk of congenital heart defects is lacking. We investigated whether folic acid supplementation in early pregnancy reduces offspring risk of heart defects in 2 large birth cohort studies. Methods and Results: Women recruited in early pregnancy within the DNBC (Danish National Birth Cohort), 1996–2003, and MoBa (Norwegian Mother and Child Cohort Study), 2000–2009, were followed until delivery. Information on periconceptional intake of folic acid and other supplements was linked with information on heart defects from national registers. Among 197 123 births, we identified 2247 individuals with heart defects (114/10 000). Periconceptional (4 weeks before through 8 weeks after conception) use of folic acid plus other supplements (54.8%), folic acid only (12.2%), and non–folic acid supplements (5.0%) were compared with no supplement use (28.0%); the adjusted relative risks of heart defects were 0.99 (95% CI, 0.80–1.22), 1.08 (95% CI, 0.93–1.25), and 1.07 (95% CI, 0.97–1.19), respectively. For initiation of folic acid in the preconception period weeks −4 to −1 (33.7%) and the postconception periods 0 to 4 weeks (15.5%), 5 to 8 weeks (17.8%), and 9 to 12 weeks (4.6%), compared with no or late folic acid intake (29.1%), relative risks of heart defect were 1.11 (95% CI, 1.00–1.25), 1.09 (95% CI, 0.95–1.25), 0.98 (95% CI, 0.86–1.12), and 0.97 (95% CI, 0.78–1.20), respectively. Relative risks of severe defects, conotruncal defects, and septal defects showed similar results. Conclusions: Folic acid was not associated with offspring risk of heart defects, including severe defects, conotruncal defects, or septal defects.

Original language	English
Article number	e011615
Journal	Journal of the American Heart Association
Volume	8
Issue number	6
Number of pages	29
ISSN	2047-9980
DOIs	https://doi.org/10.1161/JAHA.118.011615
Publication status	Published - 2019

Keywords

congenital cardiac defect
folate
MoBa (Norwegian Mother and Child Cohort Study)
pregnancy
prospective cohort study

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10.1161/JAHA.118.011615Licence: CC BY

JAHA.118.011615Final published version, 471 KBLicence: CC BY

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Øyen, N., Olsen, S. F., Basit, S., Leirgul, E., Strøm, M., Carstensen, L., Granström, C., Tell, G. S., Magnus, P., Vollset, S. E., Wohlfahrt, J., & Melbye, M. (2019). Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway. Journal of the American Heart Association, 8(6), Article e011615. https://doi.org/10.1161/JAHA.118.011615

Øyen, N, Olsen, SF, Basit, S, Leirgul, E, Strøm, M, Carstensen, L, Granström, C, Tell, GS, Magnus, P, Vollset, SE, Wohlfahrt, J & Melbye, M 2019, 'Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway', Journal of the American Heart Association, vol. 8, no. 6, e011615. https://doi.org/10.1161/JAHA.118.011615

@article{d6134840a0864b75858d92adfd8b944a,

title = "Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway",

abstract = "Background: Evidence linking individual-level maternal folic acid supplementation to offspring risk of congenital heart defects is lacking. We investigated whether folic acid supplementation in early pregnancy reduces offspring risk of heart defects in 2 large birth cohort studies. Methods and Results: Women recruited in early pregnancy within the DNBC (Danish National Birth Cohort), 1996–2003, and MoBa (Norwegian Mother and Child Cohort Study), 2000–2009, were followed until delivery. Information on periconceptional intake of folic acid and other supplements was linked with information on heart defects from national registers. Among 197 123 births, we identified 2247 individuals with heart defects (114/10 000). Periconceptional (4 weeks before through 8 weeks after conception) use of folic acid plus other supplements (54.8%), folic acid only (12.2%), and non–folic acid supplements (5.0%) were compared with no supplement use (28.0%); the adjusted relative risks of heart defects were 0.99 (95% CI, 0.80–1.22), 1.08 (95% CI, 0.93–1.25), and 1.07 (95% CI, 0.97–1.19), respectively. For initiation of folic acid in the preconception period weeks −4 to −1 (33.7%) and the postconception periods 0 to 4 weeks (15.5%), 5 to 8 weeks (17.8%), and 9 to 12 weeks (4.6%), compared with no or late folic acid intake (29.1%), relative risks of heart defect were 1.11 (95% CI, 1.00–1.25), 1.09 (95% CI, 0.95–1.25), 0.98 (95% CI, 0.86–1.12), and 0.97 (95% CI, 0.78–1.20), respectively. Relative risks of severe defects, conotruncal defects, and septal defects showed similar results. Conclusions: Folic acid was not associated with offspring risk of heart defects, including severe defects, conotruncal defects, or septal defects.",

keywords = "congenital cardiac defect, folate, MoBa (Norwegian Mother and Child Cohort Study), pregnancy, prospective cohort study",

author = "Nina {\O}yen and Olsen, {Sjurdur F.} and Saima Basit and Elisabeth Leirgul and Marin Str{\o}m and Lisbeth Carstensen and Charlotta Granstr{\"o}m and Tell, {Grethe S.} and Per Magnus and Vollset, {Stein E.} and Jan Wohlfahrt and Mads Melbye",

year = "2019",

doi = "10.1161/JAHA.118.011615",

language = "English",

volume = "8",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway

AU - Øyen, Nina

AU - Olsen, Sjurdur F.

AU - Basit, Saima

AU - Leirgul, Elisabeth

AU - Strøm, Marin

AU - Carstensen, Lisbeth

AU - Granström, Charlotta

AU - Tell, Grethe S.

AU - Magnus, Per

AU - Vollset, Stein E.

AU - Wohlfahrt, Jan

AU - Melbye, Mads

PY - 2019

Y1 - 2019

N2 - Background: Evidence linking individual-level maternal folic acid supplementation to offspring risk of congenital heart defects is lacking. We investigated whether folic acid supplementation in early pregnancy reduces offspring risk of heart defects in 2 large birth cohort studies. Methods and Results: Women recruited in early pregnancy within the DNBC (Danish National Birth Cohort), 1996–2003, and MoBa (Norwegian Mother and Child Cohort Study), 2000–2009, were followed until delivery. Information on periconceptional intake of folic acid and other supplements was linked with information on heart defects from national registers. Among 197 123 births, we identified 2247 individuals with heart defects (114/10 000). Periconceptional (4 weeks before through 8 weeks after conception) use of folic acid plus other supplements (54.8%), folic acid only (12.2%), and non–folic acid supplements (5.0%) were compared with no supplement use (28.0%); the adjusted relative risks of heart defects were 0.99 (95% CI, 0.80–1.22), 1.08 (95% CI, 0.93–1.25), and 1.07 (95% CI, 0.97–1.19), respectively. For initiation of folic acid in the preconception period weeks −4 to −1 (33.7%) and the postconception periods 0 to 4 weeks (15.5%), 5 to 8 weeks (17.8%), and 9 to 12 weeks (4.6%), compared with no or late folic acid intake (29.1%), relative risks of heart defect were 1.11 (95% CI, 1.00–1.25), 1.09 (95% CI, 0.95–1.25), 0.98 (95% CI, 0.86–1.12), and 0.97 (95% CI, 0.78–1.20), respectively. Relative risks of severe defects, conotruncal defects, and septal defects showed similar results. Conclusions: Folic acid was not associated with offspring risk of heart defects, including severe defects, conotruncal defects, or septal defects.

AB - Background: Evidence linking individual-level maternal folic acid supplementation to offspring risk of congenital heart defects is lacking. We investigated whether folic acid supplementation in early pregnancy reduces offspring risk of heart defects in 2 large birth cohort studies. Methods and Results: Women recruited in early pregnancy within the DNBC (Danish National Birth Cohort), 1996–2003, and MoBa (Norwegian Mother and Child Cohort Study), 2000–2009, were followed until delivery. Information on periconceptional intake of folic acid and other supplements was linked with information on heart defects from national registers. Among 197 123 births, we identified 2247 individuals with heart defects (114/10 000). Periconceptional (4 weeks before through 8 weeks after conception) use of folic acid plus other supplements (54.8%), folic acid only (12.2%), and non–folic acid supplements (5.0%) were compared with no supplement use (28.0%); the adjusted relative risks of heart defects were 0.99 (95% CI, 0.80–1.22), 1.08 (95% CI, 0.93–1.25), and 1.07 (95% CI, 0.97–1.19), respectively. For initiation of folic acid in the preconception period weeks −4 to −1 (33.7%) and the postconception periods 0 to 4 weeks (15.5%), 5 to 8 weeks (17.8%), and 9 to 12 weeks (4.6%), compared with no or late folic acid intake (29.1%), relative risks of heart defect were 1.11 (95% CI, 1.00–1.25), 1.09 (95% CI, 0.95–1.25), 0.98 (95% CI, 0.86–1.12), and 0.97 (95% CI, 0.78–1.20), respectively. Relative risks of severe defects, conotruncal defects, and septal defects showed similar results. Conclusions: Folic acid was not associated with offspring risk of heart defects, including severe defects, conotruncal defects, or septal defects.

KW - congenital cardiac defect

KW - folate

KW - MoBa (Norwegian Mother and Child Cohort Study)

KW - pregnancy

KW - prospective cohort study

U2 - 10.1161/JAHA.118.011615

DO - 10.1161/JAHA.118.011615

M3 - Journal article

C2 - 30857459

AN - SCOPUS:85062870132

SN - 2047-9980

VL - 8

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 6

M1 - e011615

ER -

Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway

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Keywords

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