Folic acid supplements in late pregnancy increase risk of asthma

According to CDC statistics, U.S. childhood asthma prevalence more than doubled between 1980 to the mid-1990s and has since plateaued at those historically high levels. Although many triggers and risk factors for asthma have been identified, the reasons behind this increase are not yet understood.

A recent study by University of Adelaide researchers Whitrow, Moore, Rumbold, and Davies may shed some light on the rise in asthma in young children. The study appears to show that the use of folic acid supplements in late pregnancy can lead to increased allergic asthma in children of 3.5 years of age. This human study corroborates earlier studies in mice which indicated that supplementation with folate in pregnancy leads to an allergic asthma phenotype in mice via epigenetic mechanisms (changes in gene expression).

Folic acid supplements taken in pre- or early pregnancy were not associated with asthma at any age (except as noted below). Dietary folate (from foods and vegetables, not supplements) was not associated with asthma in either age group at any stage of pregnancy.

For folate supplementation in early pregnancy, there was a decrease in the relative risk of asthma at 3.5 years of 43% for every 100-µg increase in dietary folate taken in early pregnancy if the mother had asthma herself.

For child asthma at 5.5 years, they found that for every 100-lg unit increase in dietary folate in early pregnancy, the relative risk of the child’s having asthma at 5.5 years increased by 77% if the mother smoked during early pregnancy

For every 1,000-lg increase in folic acid in late pregnancy, the relative risk
of the child’s having asthma at 5.5 years more than doubled if the mother had a previous child.

For every 1,000-lg increase in folic acid in late pregnancy, the relative risk of the child’s having asthma at 5.5 years decreased by 37% if the mother had asthma.

The authors speculate that there is a potentially important critical period of pregnancy during which supplement dosages may be manipulated to optimize the neuroprotective effects of supplemental folic acid without increasing the risk of asthma, and suggest that these results also provide testable theories to explain the rise in asthma prevalence noted internationally.

The study was conducted over 5.5 years with mothers that were recruited in the first 16 weeks of pregnancy between 1998 and 2000, prior to the introduction of folic acid fortified foods in Australia.