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

• Type of Material: Article
• Authors: NaTasha D. Hollis, Emory University; Emily Graves Allen, Emory University; Tiffany Renee Oliver, Emory University; Stuart W. Tinker, Emory University; Charlotte Druschel, New York State Department of Health; Charlotte A. Hobbs, University of Arkansas for Medical Sciences; Leslie A. O'Leary, Centers for Disease Control and Prevention; Paul A. Romitti, The University of Iowa; Marjorie H. Royle, New Jersey Department of Health and Senior Services; Claudine P. Torfs, Public Health Institute; Sallie Boineau Freeman, Emory University; Stephanie Sherman, Emory University; Lora H Bean, Emory University
• Language: English
• Date: 2013-03
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Wiley Periodicals, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.35796/abstract?systemMessage=Wiley+Online+Library+will+be+disrupted+Saturday%2C+15+March+from+10%3A00-12%3A00+GMT+%2806%3A00-08%3A00+EDT%29+for+essential+maintenance
• Title of Journal or Parent Work: American Journal of Medical Genetics Part A
• ISSN: 1552-4825
• Volume: 161
• Issue: 3
• Start Page: 438
• End Page: 444
• Grant/Funding Information: This work was supported by NIH R01 HD38979.
• Keywords: Folic acid; Chromosome segregation; Down syndrome; Meiosis; Nondisjunction; Trisomy 21; Aneuploidy
• Research Categories: Biology, Genetics; Health Sciences, Public Health

Abstract

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.