Low Levels of Vitamin B12 May Increase Risk for Neural Tube Defects
Monday, March 2, 2009
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Robert Bock or Marianne Glass Miller
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Children born to women who have low blood levels of vitamin B12 shortly before
and after conception may have an increased risk of a neural tube defect,
according to an analysis by researchers at the National Institutes of Health,
Trinity College Dublin, and the Health Research Board of Ireland.
Women with the lowest B12 levels had 5 times the risk of having a child with a
neural tube defect compared to women with the highest B12 levels.
Women who consume little or no meat or animal based foods are the most likely
group of women to have low B12 levels, along with women who have intestinal
disorders that prevent them from absorbing sufficient amounts of B12.
Neural tube defects are a class of birth defects affecting the brain and spinal
cord. One type, spina bifida, can cause partial paralysis. Another type,
anencephaly, is a fatal defect in which the brain and skull are severely
underdeveloped.
Researchers have known that taking another nutrient, folic acid, during the
weeks before and after conception can greatly reduce a woman’s chances of having
a child with a neural tube defect. Folic acid is the synthetic form of the
vitamin folate. In the United States, cereal grains are fortified with folic
acid to reduce the occurrence of neural tube defects in the U.S. population.
The study appears in the March Pediatrics. The study’s first author was Anne M.
Molloy, Ph.D., Trinity College Dublin. Scientists from the Health Research Board
of Ireland and two NIH institutes, the Eunice Kennedy Shriver National Institute
of Child Health and Human Development and the National Human Genome Research
Institute, also took part in the study.
"Vitamin B12 is essential for the functioning of the nervous system and for the
production of red blood cells,” said Duane Alexander, M.D., director of the
NICHD. "The results of this study suggest that women with low levels of B12 not
only may risk health problems of their own, but also may increase the chance
that their children may be born with a serious birth defect."
Ireland has a high rate of neural tube defects, and NIH scientists have
frequently collaborated with Irish researchers to gain insight into the causes
of this group of disorders.
To conduct the study, the researchers analyzed stored blood samples originally
collected during early pregnancy from three groups of Irish women between 1983
and 1990. During that time, pregnant women in Ireland rarely took vitamin
supplements. The study authors reasoned that the lack of routine vitamin
supplementation would allow them to identify a sufficient number of women with
low Vitamin B12 to conduct their analysis.
For their analysis, the researchers classified the women into three groups. The
first group consisted of 95 women who were pregnant with a child having a neural
tube defect at the time the blood was taken. The second group was composed of
107 women who had previously given birth to a child with a neural tube defect
but whose current pregnancy was not affected. Like the first group, women in the
third group (a total of 76) were pregnant with a child having a neural tube
defect at the time the blood sample was obtained, but were enrolled in a
different study than the women in group 1. The researchers measured the Vitamin
B12 and folate levels of the women’s blood samples, and compared them to those
of control groups whose pregnancies were unaffected by a neural tube defect.
Because low folate levels are a known risk factor for neural tube defects, the
researchers used statistical techniques to evaluate the role of Vitamin B12
independently of the role of folate. In all three groups, women with low B12
concentrations (estimated at less than 250 ng/L, before pregnancy) had 2.5-3
times the risk of having a child with a neural tube defect compared to those
with higher levels. Women with levels in the deficient range (0-149 ng/L ) were
at the highest risk: 5 times that of women with higher levels.
The study authors wrote that it is not known how B12 and folate might interact
to influence the formation of the neural tube, the embryonic structure that
gives rise to the spine and brain. They noted that the two vitamins are jointly
involved with several key biochemical reactions, as well as with the synthesis
of DNA. Lack of either Vitamin B12 or folate in any of these chemical processes
theoretically could increase the risk of a neural tube defect.
The authors noted that their results needed to be confirmed by other studies
among other populations of women. They suggested, however, that women should
have Vitamin B12 levels above 300 ng/L before becoming pregnant. (Because B12
levels drop sharply during pregnancy, the researchers adjusted the levels
measured during pregnancy to provide a target level for women to achieve before
they become pregnant.)
Because Vitamin B12 comes from foods of animal origin, women who adhere to a
strict vegan diet may be at risk for a B12 deficiency, said an NICHD author of
the paper, James L. Mills, M.D., senior investigator in the Division of
Epidemiology, Statistics, and Prevention Research. He added it is advisable for
women with digestive disorders that interfere with the absorption of foods to
consult a physician before getting pregnant, to make sure they are receiving
adequate amounts of B12.
Dr. Mills explained that critical events in the formation of the brain and
spinal column occur very early in pregnancy—in the first 28 days after
conception—before many women even realize they are pregnant.
He added that the U.S. Public Health Service recommends that all women of
childbearing age consume 400 micrograms of folic acid each day. This amount
assures that a woman will have adequate stores of the vitamin, in the event of
an unintended pregnancy.
"If women wait until they realize that they are pregnant before they start
taking folic acid, it is usually too late," Dr. Mills said.
Similarly, he said, it would be wise for all women of childbearing age to
consume the recommended amount of Vitamin B12, whether they are planning a
pregnancy or not. "Half of the women who become pregnant each year in the U.S.
were not planning to become pregnant."
"Our results offer evidence that women who have adequate B12 levels before they
become pregnant may further reduce the occurrence of this class of birth
defects," Dr. Mills said.
Vitamin B12 is available in milk, meats, poultry, eggs, as well as fortified
cereals and some other fortified foods. Information on foods that contain
Vitamin B12, as well as the Recommended Dietary Allowances for the vitamin, is
available from the NIH Office of Dietary Supplements,
http://dietary-supplements.info.nih.gov/factsheets/vitaminb12.asp
Folate is found in leafy green vegetables, fruits, and dried beans and peas.
Information on sources of folate also is available from the NIH Office of
Dietary Supplements,
http://ods.od.nih.gov/factsheets/folate.asp
Dr. Mills explains the study findings in the accompanying online video at
http://www.nichd.nih.gov/news/resources/links/videoNTDS-B12
A transcript of the video is available on the NICHD Web site at
http://www.nichd.nih.gov/news/resources/links/transcriptNTDS-B12.cfm
The NICHD sponsors research on development, before and after birth; maternal,
child, and family health; reproductive biology and population issues; and
medical rehabilitation. For more information, visit the Institute’s Web site at
http://www.nichd.nih.gov/
The National Institutes of Health (NIH) — The Nation's Medical Research Agency —
includes 27 Institutes and Centers and is a component of the U.S. Department of
Health and Human Services. It is the primary federal agency for conducting and
supporting basic, clinical and translational medical research, and it
investigates the causes, treatments, and cures for both common and rare
diseases. For more information about NIH and its programs, visit
www.nih.gov

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