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Author Notes:

Correspondence: Lora J.H. Bean, PhD, Department of Human Genetics, Emory University, 615 Michael St. Suite 301, Atlanta, GA, 30322, Phone: (404) 778-8508, Fax: (404) 727-3949, ljbean@emory.edu

Acknowledgments: The authors would like to thank the following laboratory personnel for technical assistance: Rupa Masse, Maneesha Yadav-Shaw, and Weiya He.

We would also like to thank Helen Smith and Elizabeth Sablón for family recruitment.

Additionally, we are grateful to all the personnel at each NDSP site.

Special thanks go to the many families nationwide whose participation made this study possible.

Disclosures: The authors have no conflicts of interest to declare.


Research Funding:

This work was supported by NIH R01 HD38979.


  • Down syndrome
  • Trisomy 21
  • Aneuploidy
  • Nondisjunction
  • Chromosome segregation
  • Folic acid
  • Meiosis

Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: A report from the National Down Syndrome Project

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Journal Title:

American Journal of Medical Genetics Part A


Volume 161, Number 3


, Pages 438-444

Type of Work:

Article | Post-print: After Peer Review


Both a lack of maternal folic acid supplementation and the presence of genetic variants that reduce enzyme activity in folate pathway genes have been linked to meiotic nondisjunction of chromosome 21; however, the findings in this area of research have been inconsistent. To better understand these inconsistencies, we asked whether maternal use of a folic acid-containing supplement before conception reduces risk for chromosome 21 nondisjunction. Using questionnaire data from the National Down Syndrome Project, a population-based case-control study, we compared the use of folic acid-containing supplements among mothers of infants with full trisomy 21 due to maternal nondisjunction (n=702) and mothers of infants born with no major birth defects (n=983). Using logistic regression, adjusting for maternal age, race/ethnicity, and infant age at maternal interview, we found no evidence of an association between lack of folic acid supplementation and maternal nondisjunction among all case mothers (OR=1.16; 95% CI: 0.90–1.48). In analyses stratified by meiotic stage and maternal age (<35 years or ≥ 35 years), we found an association among older mothers experiencing meiosis II nondisjunction errors (OR=2.00; 95% CI: 1.08–3.71). These data suggest that lack of folic acid supplementation may be associated specifically with MII errors in the aging oocyte. If confirmed, these results could account for inconsistencies among previous studies, as each study sample may vary by maternal age structure and proportion of meiotic errors.

Copyright information:

© 2013 Wiley Periodicals, Inc.

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