Folate Deficiency Associated with Higher Early Miscarriage Risk

Pregnant women who have low blood levels of the vitamin folate are more likely to have early miscarriages than are pregnant women who have adequate folate levels, according to a study of Swedish women by researchers at the Karolinska Institute in Sweden and at the National Institute of Child Health and Human Development (NICHD).

The finding suggests that a 1998 mandate by the U.S. Food and Drug Administration to fortify grain products with folic acid (the synthetic form of the vitamin) may prevent miscarriage in some women, in addition to lowering their risk for having a child with a class of birth defects known as neural tube defects (NTDs). NTDs include both 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.

The study appears in the current issue of the Journal of the American Medical Association. The researchers also found that women with high folate levels are no more likely to have early miscarriages than are women with moderate, but adequate, folate levels.

"The results of this study reinforce the importance of folate for women in their childbearing years," said Duane Alexander, M.D., Director of the NICHD. "Not only does taking folic acid before conception prevent the devastating form of birth defects known as neural tube defects, but it also appears to lower the risk of early miscarriage."

Since January 1998, the U.S. Food and Drug Administration has required food manufacturers to fortify certain grain products with folic acid, to reduce the risk of NTDs. Also in 1998, the Institute of Medicine recommended that all women of childbearing age receive 400 micrograms of folic acid each day. Folate occurs naturally in beans, leafy green vegetables and citrus fruits.

The study was conducted between 1996 and 1998 in Uppsala County, Sweden by Lena George, M.D., of the Karolinska Institute in Stockholm, Sweden, and her colleagues. Sweden was considered an ideal country in which to conduct this study because, unlike the United States, its grain supply is not fortified with folic acid, explained the NICHD author of the study, James Mills, M.D., of NICHD's Division of Epidemiology, Statistics, and Prevention Research. As a result, the researchers were better able to study the relationship between folate deficiency and miscarriage than they would have been in the United States, where food fortification has vastly reduced the rate of folate deficiency.

The researchers compared 468 women who had an early miscarriage (between six and twelve weeks gestation) to 921 women who were six to twelve weeks pregnant. The women were asked a series of questions about their reproductive and health histories. They also provided blood samples that were used to assess their blood folate levels and smoking status.

The researchers statistically compensated for factors known to influence miscarriage risk and blood folate level, such as maternal age, education, maternal smoking, obesity, number of previous pregnancies, and country of origin. They found that folate deficiency was associated with a fifty percent increase in risk of early miscarriage. They also found that high folate levels were not associated with miscarriage risk. The researchers defined folate deficiency as a blood folate level below 4.9 nmol/L, which is the cut-off for recommending folic acid supplements in Sweden. Women with blood folate levels between 5.0 and 8.9 nmol/L were considered to have adequate folate intakes, while women with folate levels greater than 9.0 nmol/L were considered to have high folate intakes.

Dr. Mills noted, however, American women have higher folate levels than do Swedish women. According to the 1999 CDC's National Health and Nutrition Examination Study, the average blood folate level for American women is 16.2 nmol/L.


The NICHD is part of the National Institutes of Health, the biomedical research arm of the federal government. The Institute sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD Web site,, or from the NICHD Information Resource Center, 1-800-370-2943; E-mail

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