Relationship of folic acid (FA) supplementation
and the risk of spontaneous abortion among women who

Health authorities in many countries around the world recommend women of reproductive age use folic acid supplements before and early in pregnancy to reduce the risk of having a baby with a neural tube defect.

Folic acid is the most important vitamin to take while trying to conceive for a baby’s healthy cell and neural tube development during pregnancy.

These studies about the relationship between maternal periconceptional folic acid (FA) supplementation and risk of spontaneous abortion (SA), with due consideration of the supplementation initiation timing. Women planning to conceive are advised to consume 0.4 mg folic acid tablet daily in the periconceptional period (from 3 months before conception until 12 weeks thereafter) were categorized as the FA group.

The samples in this study are 65,643 pregnancies on FA supplementation in Chongqing, China between 2010 and 2016. The result of the study shows that among the pregnancies included in the final analysis, 3,513 cases (5.35%) ended with SA shown in Table.

Compared to pregnant women in the no-FA group, women in the FA group had a lower risk of SA.

Is SA, or miscarriage, is defined in China as fetal loss before 28 gestational in 1-3 weeks. SA occurs in at least 15% of pregnancies and is strongly associated with infertility.


Further, regular FA supplementation was more common among the women who started 3 months or more prior to conception than in those who started 1-2 months before and those who started after conception. These findings indicate better compliance and a more optimal folate concentration against chromosome abnormalities and birth defects in the women who started FA supplementation earlier.

One of the possible mechanisms linking FA supplementation to the reduced risk of SA may be attributable to the role of FA in meiosis. Almost 50% of SAs result from fetal chromosomal abnormalities, of which a high proportion is caused by maternal or paternal meiosis. FA deficiency delayed the onset of meiosis and increased DNA damage in spermatocytes. Moreover, FA deficiency has been reported to possibly increase the risk for meiosis II nondisjunction errors among women aged older than 35 years.


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Hollis, NaTasha D., et al. “Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: a report from the National Down Syndrome Project.” American Journal of Medical Genetics Part A 161.3 (2013): 438-444.

Mao, Yan-Yan, et al. “Periconceptional Folic Acid Supplementation and the Risk of Spontaneous Abortion among Women Who Prepared to Conceive: Impact of Supplementation Initiation Timing.” Nutrients 12.8 (2020): 2264.

Nilsen, Roy M., et al. “Prevalence and determinants of preconception folic acid use: an Italian multicenter survey.” Italian journal of pediatrics 42.1 (2016): 1-10.