The folic acid supplements during the first trimester were associated with a 6 per cent increase in wheezing, a 9 per cent increase in infections of the lower respiratory tract, and a 24 per cent increase in hospitalisations for such infections, according to findings published in the British Medical Journal’s Archives of Diseases in Childhood.
The researchers, led by Siri Haberg from the Norwegian Institute of Public Health, speculate that the micronutrient may play a role in the development of certain immune (T) cells, which could influence the likelihood of airway inflammation in early childhood.
However, the researchers noted that the “effects were small, and unmeasured confounding may influence the associations found”.
The study’s findings may have global implications as women of child-bearing age are currently recommended to take supplements and to curb the risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants. Several countries, including the USA and Canada, have mandatory fortification of all grain products with folic acid - the synthetic, bioavailable form of folate.
Parallel fortification measures in European countries, including the UK and Ireland, are still on the table. Preliminary evidence from North America indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence.
Folate is found in foods such as green leafy vegetables, chick peas and lentils.
Haberg and her co-workers included 32,077 children up to the age of 18 months born between 2000 and 2005 in their study. The Norwegian Mother and Child Cohort Study used questionnaires to survey the dietary habits of the mothers and their intake of supplements.
A slight increase in wheezing and/or respiratory infections up to the age of 18 months was observed if mothers had taken folic acid supplements in the first three months of their pregnancy, after the results were adjusted for potential confounding factors.
A 24 per cent increase in hospital admission as a result of their infection was also observed.
Commenting on the potential mechanism, Haberg and her co-workers said that compounds like folate and folic acid act as methyl donors, meaning they affect the process of methylation (biochemical process), which in turn alters genetic activity.
They add that the impact of methylation on the immune system and respiratory diseases has not been comprehensively researched.
“Synthetic folic acid (PteGlu), the most commonly used folate form in supplements, is different from folates in food, and may act differently than natural occurring folates,” wrote the researchers.
“Absorption of PteGlu is a saturable process, and regular intake of folic acid supplements will in many subjects result in circulating unmetabolised folic acid, which may have possible effects on immune cells,” they added.
Source: Archives of Diseases in ChildhoodPublished online ahead of print, 3 December 2008; doi:10.1136/adc.2008.142448“Folic acid supplements in pregnancy and early childhood respiratory health”Authors: S.E. Haberg, S.J. London, H. Stigum, P. Nafstad, W. Nystad