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

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.

The association of low socioeconomic status and the risk of having a child with Down syndrome: a report from the National Down Syndrome Project

“…Using this same NDSP population, we have recently found that lack of folic acid supplementation around the time of conception is associated with only MII errors among older mothers. 41 …”

Maternal Age and Oocyte Aneuploidy: Lessons Learned from Trisomy 21

“…However, it is important to remember that resumption of MI occurs around ovulation, and this process may also be vulnerable to the mother's environmental exposures A next important step is to ask about environmental risk factors and their possible interaction with chiasma con fi gurations. This important work has been initiated by Ghosh et al [ 39 ] and Hollis et al [ 107 ] . These studies will be complicated by classi fi cation errors related to using observed recombination pro fi les.…”

“…Using data from the NDSP, 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) [ 107 ] . 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).…”

Present and future of developmental neuropsychopharmacology

“…Therefore the administration of choline would prevent the neonatal developmental delay in inhibition associated with attentional problems as the child matures (Ross et al, 2013). A similar example would be preconceptional administration of folic acid as the lack of this acid reduces enzyme activity in folate pathway genes, and this is related to meiotic nondisjunction of chromosome 21 (Down's syndrome) (Hollis et al, 2013).…”