1. Compared to women who did not take folate supplements, women with the highest level of folate supplementation prepregnancy had a 20% reduced risk of spontaneous abortion.
2. The inverse association was dose dependent, with higher levels of folate supplementation associated with lower risk of spontaneous abortion.
Evidence Rating Level: 2 (Good)
Study Rundown: The American College of Obstetricians and Gynecologists, the USPSTF and the CDC all currently recommend that all women of childbearing age take 400 ug/day of folic acid to prevent fetal neural tube defects. Despite this recommendation, the vast majority of women do not achieve this daily intake. Preliminary studies in animal models suggest that folate supplementation, in addition to reducing the risk of neural tube defects, may also improve embryo and fetal survival rates. However, research in humans remains inconclusive and some early studies even raising concern for an increase in miscarriage with folic acid supplementation.
In this study, researchers used data from the Nurses’ Health Study to show that women with the highest intake of supplemental folate (730 ug/day, nearly double the current recommended dose) experienced a lower risk of spontaneous abortion than women who did not take folate supplements. Strengths of this study include prospective design, large sample size and high follow-up rates. Results may be limited by recall bias due to self-reported data. Additionally, dietary intake data was only collected every four years such that participants’ folate intake may have varied over this time period. Future studies might employ a randomized design to compare rates of miscarriage among women randomized to higher doses of folate supplementation (ie 800 ug/day) to the currently recommended 400ug/day and compare birth outcomes.
Relevant Reading: Folic Acid and Miscarriage: An Unjustified Link
Study Author, Audrey J. Gaskins, ScD, talks to 2 Minute Medicine: Harvard School of Public Health
“Despite the fact that the US food supply is fortified with folic acid, the majority of US reproductive aged women consume far below the recommendation of 400 µg/day. Our study showed that prepregnancy supplemental folate intake at levels well beyond those currently recommended for the prevention of neural tube defects was not associated with increased risk of pregnancy loss; rather it may be an effective strategy to prevent spontaneous abortion.”
In-Depth [prospective cohort]: Using data from the Nurses’ Health Study II, an ongoing prospective cohort study of female nurses ages 22-44, researchers identified all women who reported at least one pregnancy from 1992-2009. Dietary and supplemental folate intake was assessed every 4 years via survey. The primary outcome was self-reported spontaneous abortion (loss at <20 weeks gestation) or stillbirth (loss at ≥20 weeks).
Of the 15,950 pregnancies reported, 2,750 (17.3%) ended in spontaneous abortion and 120 (0.8%) in stillbirth. Compared with women who consumed the least amount of folate prepregnancy (<258 ug/day), those who consumed, both via supplementation and dietary sources, the most (>851 ug/day) had a lower risk of spontaneous abortion (RR=0.91, p-trend=0.04). Women with the highest intake of supplemental folate (>730 ug/day) also had a lower risk of spontaneous abortion than those who took no folate supplementation (RR=0.80, p-trend<0.001).
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