Researchers from the University of Adelaide's Robinson Institute report that folic acid supplements taken in late pregnancy may increase the risk of asthma by about 25 per cent in children aged between 3 and 5 years, suggesting that the timing of supplementation in pregnancy is important.
"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," said lead researcher Dr Michael Davies.
Currently, supplementation with folate and folic acid - the synthetic, bioavailable form of folate - is recommended to all women of child-bearing age since most neural tube defects (NTDs), including spina bifida and anencephaly, occur within the first 22 to 28 days of pregnancy, when the mother-to-be is not aware she is even pregnant.
Folic acid supplements after this time are too late to prevent neural tube defects and therefore fail to benefit women with unplanned pregnancies - more than half of all pregnancies in the US.
The new study, published in the American Journal of Epidemiology, found that supplements in early pregnancy had no effect on asthma risk in the children, but additional folic acid during the third trimester did increase the risk of asthma.
"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," said Davies.
The Adelaide-based researchers analysed the diets and supplement use of 490 women, and measured the incidence of asthma in 423 children at 3.5 and 5.5 years. Almost 12 per cent of the children were asthmatic at both ages.
At age 3.5, the researchers found that folic acid supplements in late pregnancy were associated with a 26 per cent increased risk of childhood asthma and a 32 per cent increase in the risk of persistent asthma.
The associations were similar but not statistically significant after 5.5 years, they added.
Commenting on the implications for folic acid recommendations to reduce NTDs, Davies said: "Our study supports these guidelines, as we found no increased risk of asthma if folic acid supplements were taken in pre or early pregnancy. However, these guidelines may need to be expanded to include recommendations about avoiding use of high dose supplemental folic acid in late pregnancy."
On the flip side, no links were observed between dietary folate and asthma risk.
The link between folate and folic acid, the synthetic form of the vitamin, and respiratory health is not clear cut, with contradictory results reported in the literature. A study from Johns Hopkins Children’s Center found that higher levels of folate were associated with a 16 per cent reduction of asthma in (Journal of Allergy & Clinical Immunology, June 2009, Vol. 123, pp. 1253-1259.e2).
However, a Norwegian study reported that 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, (Archives of Diseases in Childhood, doi:10.1136/adc.2008.142448).
According to the European Federation of Allergy and Airway Diseases Patients Association (EFA), over 30m Europeans suffer from asthma, costing Europe €17.7bn every year. The cost due to lost productivity is estimated to be around €9.8bn.
The condition is on the rise in the Western world and the most common long-term condition in the UK today
According to the American Lung Association, almost 20m Americans suffer from asthma. The condition is reported to be responsible for over 14m lost school days in children, while the annual economic cost of asthma is said to be over $16.1bn.
Source: American Journal of Epidemiology
Published online ahead of print, doi:10.1093/aje/kwp315
“Effect of Supplemental Folic Acid in Pregnancy on Childhood Asthma: A Prospective Birth Cohort Study”
Authors: M.J. Whitrow, V.M. Moore, A.R. Rumbold, M.J. Davies