Red cell folate status among a subset of Canadian children with Down Syndrome post-fortification

Background Trisomy 21 or Down Syndrome (DS) is associated with altered methylation pathways. Children with DS may therefore represent a population subgroup with vulnerability to increased exposures to folic acid, which is involved in one-carbon metabolism. Folic acid (FA) fortification of flour and maternal FA supplementation are intended to reduce neural tube defects related to folate deficiency. The interventions have been widely successful in Canada. Emerging evidence suggests that higher FA exposures may also have potential negative consequences, including implications for DNA methylation. This retrospective chart review provides insight on the red blood cell (RBC) folate status of a subset of Canadian children and infants with DS, post-fortification. Methods Children with DS in two Canadian provinces were assessed in the community. Access to RBC folate testing was variable, limiting sample size to 39 (n = 27 for children <= 6 years; n = 12 for children 6-18 years). All children with DS and an RBC folate result were included. The use of FA-containing supplements and formula was documented. Results Among children 6-18 years, 100% had RBC folates >1000 nmol/L, 50% were >2000 nmol/L and 25% had levels above the upper laboratory reporting limit. Among the younger children (<6 years), 52% had RBC folates >2000 nmol and 2 children exceeded 3000 nmol/L. Among exclusively breast-fed infants (<12 months), 100% had RBC folates >1000 nmol/L and 50% had levels >2000 nmol/L, suggestive of in-utero or maternal exposures. RBC folate status among this subset of Canadian children with DS is higher than documented for the larger Canadian population, and higher than among US children with DS. Conclusions Young Canadian children with DS demonstrated high post-fortification RBC folate status. RBC folate status was higher than reported for the larger Canadian population, and higher than for US children with Down Syndrome. Consumption of folic acid-containing formula and/or supplements was relatively low among these Canadian children with DS, suggesting maternal FA supplements and/or FA-fortified foods may be important etiological factors. A larger, prospective study is needed to validate these results, and to explore potential health implications among this vulnerable population.