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Researchers in Australia have identified a link between allergic asthma in 3 to 5 year-old children and exposure to folic acid that their birth mothers took as supplements during late pregnancy. They said the timing of when folic acid is taken in pregnancy might be important.
The study was the work of Dr Michael Davies, associate professor with the Research Centre for the Early Origins of Health and Disease at the Robinson Institute in the University of Adelaide, and colleagues.
The researchers said the study may have revealed why childhood asthma has been on the rise in Australia and other developed countries over recent decades.
Davies told the press that mothers are advised to take folic acid supplements during pregnancy to prevent birth defects, but research in mice and infants suggests this may also lead to "additional and unexpected" consequences.
"In our study, supplemental folic acid in late pregnancy was associated with an increased risk of asthma in children, but there was no evidence to suggest any adverse effects if supplements were taken in early pregnancy," he added.
For the study, Davies and colleagues set out to investigate the effect of timing, dose and source of folate during pregnancy on childhood asthma.
They used data from an Australian prospective birth cohort study covering 1998 to 2005 that involved more than 500 women whose diet and supplements were assessed by food frequency questionnaire in early ( before 16 weeks) and late (between 30 to 34 weeks) pregnancy, and whose children’s asthma status was followed up at 3.5 and 5.5 years.
 

The results showed that:
   

* Asthma was reported in 11.6 per cent of children at 3.5 years and 11.8 per cent of children at 5.5 years.
    * Nearly a third of these children reported persistent asthma.
    * Folic acid taken in supplement form in late pregnancy showed a statistically significant association with an increased risk of
childhood asthma at 3.5 years.
    * There was a similarly statistically significant link to an increased risk of persistent asthma at 3.5 years.
    * The links were just as strong when the researchers accounted for potential confounders.
    * There was a similar but not statistically significant link at 5.5 years.
    * Nearly half of all mothers in the study took a folic acid supplement pre-pregnancy and 56 per cent met the required daily public
health recommended dosage of 400 micrograms in early pregnancy.

The authors concluded that:
 

"These findings on childhood asthma support previous observations that supplementation with folate in pregnancy leads to an allergic asthma phenotype in mice via epigenetic mechanisms and is associated with poorer respiratory outcomes in young children."
Public health guidelines currently recommend that women supplement their diet with 400 micrograms of folic acid per day in the month leading up to and during the first trimester of pregnancy to reduce the risk of neural tube defects in children.
Davies said this study supports this guideline, because they found no increased risk of asthma when the folic acid supplements were taken before or early in pregnancy.
"These findings show there is a potentially important critical period during which folic acid supplement dosages may be manipulated to optimise their neuro-protective effects while not increasing the risk of asthma," he said.
"However, these guidelines may need to be expanded to include recommendations about avoiding use of high dose supplemental folic acid in late pregnancy," added Davies.
He also emphasized that they found no evidence that asthma was linked to folate found naturally in foods like green leafy vegetables, some fruits and nuts.