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Plasma Folate Levels and Risk of Spontaneous Abortion
Lena George, MD;
James L. Mills, MD,MS;
Anna L. V. Johansson, MSc;
Anna Nordmark, MSc;
Bodil Olander, MD;
Fredrik Granath, PhD;
Sven Cnattingius, MD,PhD
JAMA. 2002;288:1867-1873.
Context Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies.
Objective To study the association between plasma folate levels and the risk of spontaneous abortion.
Design, Setting, and Population Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks.
Main Outcome Measure Risk of spontaneous abortion vs maternal plasma folate level.
Results Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low ( 2.19 ng/mL [4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and  6.17 ng/mL [14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33).
Conclusion Low plasma folate levels were associated with an increased risk of early spontaneous abortion.
Author Affiliations: Department of Medical Epidemiology (Drs George, Granath, and Cnattingius, and Ms Johansson) and Department of Medical Laboratory Sciences and Technology (Ms Nordmark), Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden; Pediatric Epidemiology Section, Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md (Dr Mills); and Department of Clinical Chemistry, Karolinska Laboratoriet, Danderyds Hospital, Stockholm (Dr Olander).
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