Two studies presented at a recent meeting of the American Academy of Allergy, Asthma and Immunology show high folate levels in utero may increase a child’s future asthma risk, prompting reconsideration of a government decision that led to unexpected results.
In 1996, the United States Department of Agriculture required that cereals and grains be fortified with folic acid in an effort to prevent spinal bifida and anencephaly. According to Siri E. Haberg, M.D., Ph.D., of the Norwegian Institute of Public Health in Oslo, one of the two presenters of the study results, second trimester maternal folate levels over 17.84 nmol/L were associated with 66 percent elevated risk of the child having asthma at 3 years of age.
‘Benefits Still Outweigh Risks’
“We do not recommend women to stop taking folic acid supplements based on current studies of asthma and allergy. Women should follow the current guidelines until we have more knowledge, since folic acid decreases the risk of neural tube defects,” Haberg stated.
The American study group, led by Dr. Adesua Y. Okupa of the University of Wisconsin-Madison, found children’s own folate levels at age 4 had little correlation with development of asthma by age 6. Women in the highest folate quintile had the significant 66 percent elevated risk of their child having asthma as a toddler.
Dr. Elizabeth Matsui of the Department of Pediatrics at Johns Hopkins in Baltimore says she thinks this research is premature.
“The mechanism explaining how folic acid might increase a child’s risk of asthma or allergies is unknown. Some scientists have speculated that folic acid might encourage silencing of some genes involved in asthma or allergies, but this is only speculation,” said Matsui. “The benefits of taking folic acid supplements during pregnancy still far outweigh the risks.”
Preventing Birth Defects
“Pregnant women should continue to take folate during pregnancy, as it’s been shown to prevent birth defects. We and others, however, are investigating the potential side effects of folate during pregnancy. While we know that folate affects the risk of asthma in mice, we are still looking into the effects of folate in humans,” explained Dr. David Schwartz, provost of the University of Colorado School of Medicine and Director of the Center for Genes, Environment, and Health in Denver, CO.
According to Schwartz, the findings from all studies to date regarding folic acid and asthma and allergies come from observational studies and thus are not conclusive at this point.
“Findings from observational studies should not be used to alter the current recommendations regarding folic acid supplementation and fortification,” Schwartz said. “A study in mice shows that supplemental folate affects the methylation of DNA and this causes an asthma-like phenotype in mice. The two subsequent epidemiological studies in humans show that supplemental folate during pregnancy increases the risk of asthma.”
Overuse Could Pose Risks
However, Michael Davies, co-director of the Research Centre for the Early Origins of Health and Disease at the Robinson Institute at the University of Adelaide, Australia, argues that if the purpose of taking folic acid is to reduce the risk of neural tube defects in offspring, there is no benefit from supplementing past the first trimester.
“The critical period of development has passed and cannot be altered. Continued supplementation increases the risk of asthma in offspring,” Davies said. “There is also a dose-response relationship—apart from the timing of consumption, there is the risk of exposure to unmetabolised folic acid, as there is a threshold for our bodies to process folic acid.”
“Some common preparations have several times this amount. We do not yet know the consequences of this in humans—however, the effects in animals on gene expression in the fetus are concerning,” Davies said.
Further Study Called For
Although Davies agrees continued supplementation may be warranted if a woman is using certain prescription medications that can reduce blood folate levels, he maintains further study is needed.
“We don’t have sufficient data to quantify this tradeoff as yet. We need further replication of the finding elsewhere, and longer-term follow-up of our children,” Davies said.
“This is in my opinion a research finding that has not been sufficiently studied to give public advice. It remains to be seen whether it can be replicated by others,” said Per Magnus, director of the Division of Epidemiology at the Norwegian Institute of Public Health.
Calling for Reexamination
Davies and Schwartz say the government’s original decision to have pregnant women take folic acid, was justified despited the possible unexpected ramifications on children’s health.
“Past advice was made on the basis of the best available evidence,” Davies said. “Our findings don’t contradict current recommendations on periconceptional folic acid supplementation. However, marketing of prolonged high dose supplementation will need critical reexamination.”
“The government’s decision was a good decision based on the available evidence that folate prevents neural tube and craniofacial birth defects,” added Schwartz.
“We are now entering a very exciting phase of science in which we will be able to understand the complex and dynamic interplay of genes, environment, and the acquisition of chronic disease risk during early human development,” Davis said. “Our study was one of the first to show this potential interplay with regard to a very common disease. We look forward to engaging with funding bodies and the community in the study of many more.”
Tabassum Rahmani ([email protected]) writes from Dublin, California.