Low Folate Levels and Increased Risk of Miscarriage
The B vitamin folate, also called folic acid, is a water-soluble vitamin that plays a critical role in DNA formation and regulation. For this reason, it has been suggested that the rapidly developing cells in a human embryo might by damaged by a lack of adequate folate, possibly leading to miscarriages. Research has already shown that folate deficiencies during pregnancy can lead to neural tube defects in babies, leading the US Food and Drug Administration to require that foods—like flour, rice, and cornmeal—be fortified with the vitamin.
However, there has been conflicting evidence about whether folate supplementation is beneficial for preventing miscarriages. Some researchers have even speculated that high levels of folate could actually increase the risk of miscarriage.
New research in the October 16, 2002 Journal of the American Medical Association sheds light on this controversy. Researchers in Sweden (a country that does not fortify their food with folate) found that women with low blood levels of folate were more likely to have a miscarriage than women with higher folate levels. Not only did the researchers show that higher folate levels did not increase the risk of miscarriage, the research suggested that high blood folate levels could even be protective.
About the Study
Researchers from Huddinge University Hospital in Stockholm, Sweden and the National Institute of Health studied 1389 Swedish women over a 2-year period. All study participants were recruited from the Department of Obstetrics and Gynecology at Uppsala University Hospital in Uppsala County, Sweden – the only place in that county that cares for women with miscarriages. Women were eligible as cases if they had a miscarriage at 6 to 12 weeks of gestation. Women in the comparison group included those who were pregnant and carried their babies to term and those who had an induced abortion. (Note: The researchers included the women who were planning to have an induced abortion to the comparison group to make sure the sample was representative of the Swedish population.)
All women were interviewed in person using a structured questionnaire – most within 2 weeks after a miscarriage diagnosis or last completed week of gestation. Women were asked about possible risk factors for miscarriage including age, previous reproductive history, smoking, caffeine and alcohol use, shift work, prescription drug use, pregnancy symptoms (like nausea, vomiting, and fatigue), and daily intake of folic acid supplements.
Blood samples were collected and all women were categorized according to their blood folate levels. Blood cotinine levels were measured to determine exposure to cigarette smoke, and the researchers also looked at genetic factors that might affect the risk of a miscarriage. When available, researchers also collected samples of tissue from miscarriages to look at the association between plasma folate levels and risk of miscarriages caused by chromosome (genetic) abnormalities.
During the 2-year study period, a total of 468 women had miscarriages. Women with low plasma folate levels were 47% more likely to have a miscarriage, while those with higher folate levels showed no increased risk of miscarriage. Low folate levels were also associated with a significantly increased risk of miscarriage when the fetal chromosomes were abnormal, but not when the chromosomes were normal or unknown.
Adjustments were made for maternal age, cigarette smoking, average caffeine intake, previous miscarriage, education, number of children birthed, country of birth, body mass index, change of eating habits, and pregnancy symptoms like nausea, vomiting and fatigue.
Although these results are compelling, there are some limitations to this study. First, the results may not be entirely applicable to American women. Only about 5% of the pregnant women in the study took folic acid supplements, which many US women take during and just before pregnancy. In addition, foods in Sweden are not fortified with folate as they are in the US. It may be, therefore, that American women have generally higher levels of folate than their Swedish counterparts. Second, miscarriages occurring before 6 weeks’ gestation would not have been included in this study. Third, women who had miscarriages may recall their risk factors differently than those who did not miscarry. It is also possible that women whose folate levels were higher also have other characteristics affecting their overall health and their ability to carry a baby to term. Finally, because the genetic analysis was not performed for all women who had miscarriages, the findings regarding a link between genetic abnormalities and folate levels should be interpreted with caution.
How Does This Affect You?
Should you take folate supplements if you’re pregnant or thinking of becoming pregnant? Absolutely. Research has already shown that the risk of neural tube defects is reduced 50% to 70% if women take 400 micrograms of synthetic folic acid every day. This new research supports the theory that folate may also reduce your risk of miscarriage. Some research also suggests that folic acid may have other health benefits, including protection against heart disease, cervical and colon cancer, and possibly breast cancer.
In addition to taking a folic acid supplement, here are some other steps you can take to increase your chances of having a healthy baby:
- Don’t smoke, drink alcohol, or use illegal drugs while you’re pregnant
- Eat a healthful, balanced diet
- Maintain a healthy weight
- Get prenatal medical care
March of Dimes
American College of Obstetricians and Gynecologists
George L, Mills JL, Johansson AL, et al. Plasma folate levels and risk of spontaneous abortion. JAMA. 2002;288:1867-1873.
Torpy JM. Miscarriage. JAMA. 2002;288:1936.
Last reviewed Oct 18, 2002 by
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