Periconceptional folic acid supplementation and the risk of preterm births in China: a large prospective cohort study

Int J Epidemiol. 2014 Aug;43(4):1132-9. doi: 10.1093/ije/dyu020. Epub 2014 Mar 5.


Background: Folic acid-containing multivitamins have been associated with a reduced risk of preterm birth. We examined whether periconceptional use of folic acid alone reduced this risk.

Methods: Data were derived from a large population-based cohort study conducted in China to evaluate the prevention of neural tube defects with folic acid supplementation. The sample comprised 207 936 singleton live births delivered at gestational ages of 20-42 weeks to women from two provinces in southern China. Healthcare workers recorded folic acid intake prospectively each month. Gestational age calculation was based on the first day of the last menstrual period. Preterm births were categorized into three clinical subtypes: iatrogenic preterm birth, preterm premature rupture of membranes (PPROM) and spontaneous preterm birth. Logistic regression was used to evaluate the association between folic acid use and the risk of preterm birth, adjusting for potential confounders.

Results: The incidence of preterm birth was significantly lower among folic acid users (5.28%) than among non-users (6.10%). Folic acid use showed a 14% risk reduction for preterm birth overall [adjusted risk ratio (RR) = 0.86, 95% confidence interval (CI) 0.82-0.90]. This association was strongest for spontaneous preterm birth (adjusted RR = 0.81, 95% CI 0.78-0.86) and was not significant for iatrogenic preterm birth (adjusted RR = 0.97, 95% CI 0.88-1.07) or PPROM (adjusted RR = 1.07, 95% CI 0.93-1.23).

Conclusions: Daily intake of 400 μg folic acid alone during the periconceptional period was associated with a reduced risk of spontaneous preterm birth.

Keywords: Folic acid; cohort study; iatrogenic preterm birth; periconceptional supplementation; preterm premature rupture of membranes; spontaneous preterm birth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • China / epidemiology
  • Cohort Studies
  • Female
  • Fertilization*
  • Fetal Membranes, Premature Rupture / epidemiology*
  • Folic Acid / therapeutic use*
  • Humans
  • Logistic Models
  • Neural Tube Defects / prevention & control*
  • Preconception Care
  • Pregnancy
  • Premature Birth / epidemiology*
  • Prenatal Care
  • Prospective Studies
  • Vitamin B Complex / therapeutic use*
  • Young Adult


  • Vitamin B Complex
  • Folic Acid