Moderate maternal folic acid intake may improve hypermethylation at birth

VANCOUVER, BRITISH COLUMBIA — When daily intake remained below 1,200 mcg per day, periconceptional folic acid supplementation lowered an infant’s methylation fractions at the insulin-like growth factor II/H19 differentially methylated region, according to data presented at the 2010 Pediatric Academic Societies Meeting.

Cathrine Hoyo, PhD, MPH, of Duke University in Durham, N.C., and colleagues collected information through a standardized questionnaire on the periconceptional and prenatal folic acid use of 438 pregnant women who gave birth between 2004 and 2009. Hoyo said the researchers also used pyrosequencing at birth to measure cord blood methylation fractions at CpG dinucleotides of two differentially methylated regions (DMRs) previously associated with loss of IGF-II imprinting.

Among the infants whose mothers reported no folic acid supplementation, results indicated that the average methylation fraction was about 61%, which was considerably higher than the normal 50%, at the DMR upstream of H19 (range, 57% to 63.3%).

The researchers also noted decreased methylation toward the normal 50% at this DMR in infants of mothers taking less than 1,000 mcg of folic acid daily (P=.04) when compared with infants of mothers not taking folic acid, according to Hoyo. Infants whose mothers were taking 1,000 mcg to 1,200 mcg of folic acid per day had even lower methylation fractions (P<.0001). A reported daily intake of more than 1,200 mcg of folic acid, however, was linked to substantially higher methylation fractions, Hoyo said.

Hoyo also noted that this relationship between folic acid and methylation fractions appeared to be the same whether supplementation was periconceptional or prenatal.

The researchers observed no association between these results and birth weight, gestational age, birth order, race, sex and maternal age.

“What these results suggest is that maybe H19 or maybe other regulatory sequences that regulate imprinting genes may actually be very good targets because not only are they responsive to environmental cues, but they also have this way of keeping that record of experience up until the time people are 16 years old,” Hoyo said at the meeting. – Melissa Foster

For more information:

Hoyo C. #1160.2. Presented at: 2010 Pediatric Academic Societies Annual Meeting; May 1-4, 2010; Vancouver, British Columbia.

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