The study, which appeared in the December 6 issue of The Lancet, was led by Sean Daly,
of Coombe Women's Hospital in Dublin (now at Thomas Jefferson Hospital in Philadelphia,
PA). The research team also included members from the NICHD, from Trinity College in
Dublin and from the Health Research Board of Ireland.
Briefly, the study treated a group of women of childbearing age with different doses of
folic acid (0, 100, 200, or 400 micrograms) for 6 months to determine how much was needed to
raise their blood folate to a level known to protect against most neural tube defects. The
researchers found women receiving 100 micrograms reached a level that would prevent 22
percent of NTDs. The women receiving 200 micrograms did even better; they reached a level
that would prevent 41 percent of NTDs.
Neural tube defects (NTDs) are a class of birth defects affecting the brain or spinal cord.
They occur in about one per thousand pregnancies in the U.S. each year. Among the most
common NTDs are spina bifida, in which a piece of the spinal cord protrudes from the spinal
column, causing paralysis below the protrusion, and anencephaly, a fatal condition in which the
brain fails to develop normally.
Experts believe that around 50 percent of neural tube defects can be prevented by folic
acid and that 200 micrograms a day is a highly effective dose. Previous studies have found that
women who take folic acid shortly before and just after they conceive a child are less likely to
give birth to a child with an NTD, according to a member of the research team, James L. Mills,
MD, Chief of the NICHD's Pediatric Epidemiology Section.
In addition, the United States Public Health Service currently recommends that all
women of childbearing age take a 400 microgram folic acid supplement each day; however, this
recommendation is not widely followed. (Folic acid is the form found in vitamin pills; folate is
the natural form found in foods.)
Because women are not getting the recommended supplements, the FDA has instituted a
program to fortify food with folic acid. By January 1, 1998 , 140 micrograms of folic acid will
be added to every 100 grams of grain. This dose should assure an increase of 100 micrograms in
the diet of the average woman of childbearing age.
Thus, this study is important for two reasons, Dr. Mills explained. First, it demonstrates
for the first time that 100 micrograms will be sufficient to prevent many NTDs. Second, it
demonstrates that 200 micrograms will prevent most of the NTDs that are possible to prevent
Experts have been concerned that, on one hand, the current food fortification plan would
not provide enough folic acid to prevent NTDs, and on the other that increasing the level of
fortification might not be safe for heavy consumers of grain products. Higher levels of
fortification could expose some people to over 1000 micrograms per day. This level could make
it difficult to diagnose pernicious anemia in the elderly. Pernicious anemia results from a lack of
ability to absorb vitamin B12. Untreated, it can result in severe nerve damage. Doctors often
make the diagnosis because of a particular type of anemia; large doses of folic acid can prevent
the anemia, making the diagnosis more difficult, while the neurologic damage progresses.
Currently, the National Academy of Sciences' recommended daily allowance (RDA) for
folic acid is 400 micrograms per day for pregnant women and 180 micrograms for other adult
women and 200 micrograms for male adults.
Dr. Mills explained that the most definitive way for estimating how much folic acid is
needed to prevent NTDs would be to assign women who were trying to conceive a child to one
of several groups receiving various doses of folic acid, and to observe how large a dose would be
needed to prevent the NTDs. It would be unethical to do this, however, as giving women only a
small amount of folic acid might deny them the protection folic acid provides against conceiving
a child with an NTD.
Dr. Mills added that earlier studies have measured the folate levels in the red blood cells
of both women who have conceived children having an NTD, and of women whose children did
not have an NTD. From these measurements, researchers have been able to construct estimates
of a woman's chances of having a child with an NTD, based on her red cell folate levels around
the time of conception.
In their study, the Irish and American researchers recruited 100 women of childbearing
age and randomly assigned them to receive either a placebo or 100 micrograms, 200 micrograms,
or 400 micrograms of folic acid each day for 6 months. Women were not allowed to take part in
the study if they were pregnant, planning to become pregnant during the study, or believed that
they might soon become pregnant.
At the end of the study period, the researchers measured the folate levels in red blood cell
samples the women had provided. Based on these measurements, the women receiving 100
micrograms of folate a day would have decreased their risk of having a child with an NTD by 22
percent, the women receiving 200 micrograms would have a 41 percent decreased risk, and the
women in the 400 microgram group would have a 47 percent decreased risk. The researchers
added that increasing folate intake by 100 micrograms a day for longer than 6 months could
possibly reduce the risk of NTDs by an even greater amount.
Women who have already conceived a child with an NTD are considered to be at high
risk for conceiving other children with NTDs. Dr. Mills noted that this study could not assess
whether the 100 microgram increase would be effective in reducing the incidence of NTDs born
to women in this group, as there were not enough high-risk women available to take part in the
study. Such high-risk women should take 4 milligrams (4000 micrograms) of folic acid each day
prior to becoming pregnant.