Pregnancy B12 Levels Associated With Neural Tube Defects


A low vitamin B12 blood level was an independent and significant risk factor for having a pregnancy affected by a neural tube defect in a study of Irish women, in what the authors say is the first study to examine the risk of the birth defect associated with maternal B12 concentration.

Their results have public health implications in terms of possible fortification of grains with B12, although more studies are needed to learn more about the safety of this approach and the optimal protective dose of B12 in food, according to Anne M. Molloy, Ph.D., of Trinity College, Dublin and her associates.

The data indicated that most of the neural tube defect (NTD) risk was limited to maternal B12 levels at approximately 250 ng/L or less, although the data suggested that the risk could be further lowered if the B12 level was above 320–350 ng/L. Based on this, they recommended that women have a vitamin B12 level above 300 ng/L before conceiving.

The other authors were from the Child Health Epidemiology Unit at the Health Research Board in Dublin; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health and the National Human Genome Institute at NIH (Pediatrics 2009;123:917–23). Because the neural tube defect rate in Ireland is high, NIH and Irish researchers have worked together on NTD studies.

The study compared B12 levels in stored blood samples of three groups of Irish women, at a median 15 weeks' gestation, obtained between 1983 and 1990, before food was fortified with folic acid and when vitamin supplementation during pregnancy in Ireland was not common. Mandatory folic acid fortification of grains in the United States has been reported to have reduced the incidence of NTDs by as much as 78%. But folic acid cannot prevent all NTDs and low maternal B12 has previously been associated with a risk of NTDs, the authors wrote.

The three groups were composed as follows: 95 women with a pregnancy affected by a NTD (mean age 27 years) and 265 controls with a normal pregnancy (mean age 28 years); 107 women who had had a previous pregnancy affected by an NTD but were pregnant again with an unaffected pregnancy (mean age 32 years) and 414 controls (mean age 28 years); 76 women during an affected pregnancy (mean age 27 years); and 222 controls (mean age 28 years).

When compared with controls, the B12 levels were significantly lower among the women who had a pregnancy affected by a NTD, with levels below 250 ng/L associated with the greatest risk. The risk of having a pregnancy affected by an NTD was three times greater among women with B12 concentrations below 200 ng/L, compared with those whose levels were above 400 ng/L. The median B12 concentrations among the affected women in all three groups were 13%-19% lower than those with unaffected pregnancies, a significant difference.

Since B12 values were obtained at a median 15 weeks' gestation, at which time the level naturally would have dropped by about 20%-25%, “our data indicate that women should aim to enter pregnancy” with serum B12 concentrations above 300 ng/L,” the authors concluded, adding that concentrations above 400 ng/L “might be desirable, although we found no statistically significant benefit,” for that value.

The researchers did an analysis to determine if the effects of B12 and folate on NTD risk were independent, which found “little interaction between B12 and folate,” they said. Mandatory fortification of grain products in the United States with folic acid, the synthetic version of the vitamin folate, has been reported to reduce NTD incidence by as much as 78%. But, “it is generally agreed that not all NTDs are preventable by folic acid.”

In a statement issued by NICHD, Dr. James Mills, one of the authors and a senior investigator in the NICHD's division of epidemiology, statistics, and prevention research, pointed out that since dietary B12 is contained in milk, poultry, and other animal sources, women who are on a strict vegan diet may be at an increased risk of an NTD. He also advised that women with intestinal disorders who may not absorb an adequate amount of B12 should consult with physicians before pregnancy, to ensure that they are getting enough of this vitamin.

The authors had no relevant disclosures.

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