How to Cite this Article: Hollis ND, Allen EG, Oliver TR, Tinker SW, Druschel C, Hobbs CA, O'Leary LA, Romitti PA, Royle MH, Torfs CP, Freeman SB, Sherman SL, Bean LJH. 2012. Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: A report from the National Down Syndrome Project. Am J Med Genet Part A 161A: 438–444.
Article first published online: 7 FEB 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 3, pages 438–444, March 2013
How to Cite
Hollis, N. D., Allen, E. G., Oliver, T. R., Tinker, S. W., Druschel, C., Hobbs, C. A., O'Leary, L. A., Romitti, P. A., Royle, M. H., Torfs, C. P., Freeman, S. B., Sherman, S. L. and Bean, L. J.H. (2013), Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: A report from the National Down Syndrome Project. Am. J. Med. Genet., 161: 438–444. doi: 10.1002/ajmg.a.35796
The authors have no conflicts of interest to declare.
- Issue published online: 21 FEB 2013
- Article first published online: 7 FEB 2013
- Manuscript Accepted: 1 NOV 2012
- Manuscript Received: 31 MAY 2012
- NIH. Grant Number: R01 HD38979
- Down syndrome;
- trisomy 21;
- chromosome segregation;
- folic acid;
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 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. © 2013 Wiley Periodicals, Inc.