The beneficial effect of
folic acid supplementation before and shortly after conception is well recognized, whereas the effect of supplementation during the second and third trimesters is controversial and poorly documented. Our aims were to systematically review randomized controlled trials (RCTs) investigating the effect of
folate supplementation on
birth weight, placental weight and length of gestation and to assess the dose-response relationship between
folate intake (
folic acid plus dietary
folate) and health outcomes. The MEDLINE, EMBASE and Cochrane Library CENTRAL databases were searched from inception to February 2010 for RCTs in which
folate intake and health outcomes in pregnancy were investigated. We calculated the overall intake-health regression coefficient (β^) by using random-effects meta-analysis on a log(e)-log(e) scale. Data of 10 studies from 8 RCTs were analyzed. We found significant dose-response relationship between
folate intake and
birth weight (P=0.001), the overall β^ was 0.03 (95% confidence interval (CI): 0.01, 0.05). This relationship indicated 2% increase in
birth weight for every two-fold increase in
folate intake. In contrast, we did not find any beneficial effect of
folate supplementation on placental weight or on length of gestation. There is a paucity of well-conducted RCTs investigating the effect of
folate supplementation on health outcomes in pregnancy. The dose-response methodology outlined in the present systematic review may be useful for designing clinical studies on
folate supplementation and for developing recommendations for pregnant women.