Thursday March 5 2009
Babies whose mothers lack vitamin B12 are more likely to have defects
“Women who are strict vegetarians or vegans may be at greater risk of having a child with birth defects,” The Daily Telegraph has reported, saying that a lack of vitamin B12 appeared to be responsible. The newspaper says research conducted in Ireland has found that women who have low levels of the vitamin when they conceive are at greater risk of having a child with neural tube defects, such as spina bifida.
Women are already advised to take folic acid supplements when trying to conceive because the vitamin protects against neural tube defects. It is now suggested that taking vitamin B12 may reduce the risk further. In this research, scientists looked specifically at a group of women who were not taking vitamin supplements. This was to evaluate the effect of B12 levels independently from the known effect of folic acid. It was found that women with the lowest B12 levels had a two to three times greater chance of having a baby with a neural tube defect.
Looking at the role of B12 alone adds to the reliability of this research. Before B12 can be recommended for general use, experimental studies such as randomised trials will be needed to assess the effect of taking folate and B12 together. This research did not specifically look at vegan or vegetarian diets, although these regimes avoid milk, meat and eggs, which are all sources of vitamin B12.
Where did the story come from?
This research was conducted by Dr Anne M. Molloy from the School of Medicine at Trinity College in Dublin, along with colleagues from elsewhere in Ireland. The study was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and the Health Research Board (Ireland). The study was published in Pediatrics, the peer-reviewed medical journal of the American Academy of Pediatrics.
What kind of scientific study was this?
This was an analysis of data from three nested case control studies collected from 1983 to 1990, looking at levels of vitamin B12 in pregnant women and their chances of having a baby with neural tube defects.
Neural tube defects are thought to occur if there is interference with the closure of the neural tube in the embryo at around the 28th day after fertilisation. Conditions such as spina bifida and anencephaly are examples of these defects. Folic acid fortification of grain products is mandatory in the US, and recommended as a form of vitamin supplementation in the UK. The practice has been shown to reduce the number of babies born with these defects.
The researchers say that folic acid supplementation can prevent about 50% to 70% of neural tube defects, and that vitamin B12 interacts closely with folate metabolism. Other studies have also found low vitamin B12 status in mothers of children affected by neural tube defects. Because not all babies born with neural tube defects have mothers who are deficient in folate, this research focused on whether a lack of vitamin B12 could explain the remaining neural tube defects (30 to 50%).
The researchers measured the vitamin B12 levels in blood samples taken from pregnant Irish women. These were taken at an average of 15 weeks of pregnancy in three independent groups of women whose pregnancies were affected by neural tube defects, or who had had a previous baby with such a defect. These women were used as the cases in the study.
These cases were compared with a control group of women taken from the same populations as the cases, but who did not have a baby with the condition. All three case control studies were done at a time when vitamin supplementation and food fortification were rare.
In these three groups, the blood samples were taken as follows:
- Group 1 blood samples were taken from 95 women during a neural tube defect–affected pregnancy, and 265 control subjects.
- Group 2 included blood samples from 107 women who had a previous neural tube defect birth but whose current pregnancies were not affected, as well as 414 control subjects.
- Group 3 samples were taken from 76 women whose pregnancies were affected by neural tube defects, as well as 222 control subjects.
Blood samples for Vitamin B12, serum folate, and the folate content of red cells were all collected at around 15 weeks of pregnancy. Levels were measured between three and nine years from the date of sample collection, with each group analysed as a batch so as to ensure that samples from cases and controls were randomly mixed so that operators were not aware of the sample status.
A statistical technique known as logistic regression modelling was used to test whether decreasing levels of B12 was a significant risk for neural tube defects in each of the groups. Adjustments were made for the year the samples were taken, as well as for folate status.
What were the results of the study?
The researchers say that mothers of children affected by neural tube defects had significantly lower B12 status. Adjusted odds ratios showed that in all three groups the quartile of women with the lowest B12 levels had a two to three-fold chance of their child having a neural tube defect compared to women with the highest B12 levels. Pregnancy blood B12 concentrations of less than 250 nanograms per litre had with the highest risks.
What interpretations did the researchers draw from these results?
The researchers say that deficient or inadequate maternal vitamin B12 status is associated with a significantly increased risk for neural tube defects. They suggest that women should have vitamin B12 levels of more than 300 ng/L (221 pmol/L) before becoming pregnant. Improving B12 status beyond this level may afford a further reduction in risk, but this is uncertain.
What does the NHS Knowledge Service make of this study?
As the authors claim, this study is probably the first to examine the risk of having a baby born with these defects as a result of B12 deficiency. It has shown that, in three separate groups, low B12 levels are an independent maternal risk factor for having a baby affected by a neural tube defect.
This independence is an indication that folate and vitamin B12 are each acting in their own ways but, as the authors say, the two are also be acting together to some extent. They say that this is because women in the bottom quarter of both plasma folate and B12 measurements had a more than five times greater risk of a birth affected by neural defects than those in the highest quartile.
This study was also large enough to detect an average B12 difference of 15%, and this allowed the researchers to estimate the level of B12 required to prevent neural tube defects.
There are other points to note:
- The diets of the women, particularly the number of women who were vegans or vegetarians, were not evaluated by the researchers, as implied by the news reports. Although it is known that these diets are deficient in both the vitamins, the number of women in the affected and control groups of this study who avoided meat, eggs or milk is not reported.
- The studies were carried out within a population in Ireland that had a high risk of neural tube defects, and at a time when women were not exposed to prenatal vitamin supplementation. The advantage of this is that the size of the effect observed might be greater. But on the other hand, it may limit the applicability of this study to lower risk populations in times when flour fortification or vitamin supplementation are routine.
- The researchers also acknowledge that the study was limited by a lack of demographic data on participants, for example, maternal age, number of pregnancies, and the lack of red cell folate data. Red cell folate is a more accurate measure of folic acid status, particularly for women in the Group 1 study. This may have been more informative than the serum folate measurements.
Overall, this study provides an important direction for future research into how neural tube defects might be further reduced. Case control studies can never completely control for unknown or unmeasured differences between the case and control groups. The interaction of folic acid and vitamin B12 will need further testing in randomised trial designs before a general recommendation can be made.