The results from epidemiologic studies linking blood
folate concentrations,
folic acid supplementation, or dietary
folate to the risk of
preterm birth are inconsistent. In this study, we aimed to summarize the available evidence on these associations. A systematic search of the PubMed/MEDLINE, Google Scholar, Web of Science, and Cochrane Library databases up to October 20, 2018 was performed and reference lists of retrieved articles were screened. Pooled odds ratios (
ORs) and 95% confidence intervals (CIs) for the highest vs. the lowest levels of
folate concentrations,
folic acid supplementation, and dietary
folate were calculated using random-effects models. Subgroup analyses and univariate meta-regression were performed to explore the sources of heterogeneity. Ten studies (six prospective cohort studies and four case-control studies) were included on
folate concentrations, 13 cohort studies were included about
folic acid supplementation, and 4 cohort studies were included regarding dietary
folate intake. Higher maternal
folate levels were associated with a 28% reduction in the risk of
preterm birth (OR 0.72, 95% CI 0.56-0.93). Higher
folic acid supplementation was associated with 10% lower risk of
preterm birth (OR 0.90, 95% CI 0.85-0.95). In addition, a significant negative association was observed between dietary
folate intake and the risk of
preterm birth (OR 0.68, 95% CI 0.55-0.84), but no significant relation was seen between dietary
folate and the risk of spontaneous
preterm birth (OR 0.89, 95% CI 0.57-1.41). In the subgroup analysis, higher maternal
folate levels in the third trimester were associated with a lower risk of
preterm birth (OR 0.58, 95% CI 0.36-0.94). To initiate taking
folic acid supplementation early before conception was adversely associated with
preterm birth risk (OR 0.89, 95% CI 0.83-0.95). In conclusion, higher maternal
folate levels and
folic acid supplementation were significantly associated with a lower risk of
preterm birth. The limited data currently available suggest that dietary
folate is associated with a significantly decreased risk of
preterm birth.