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Minerva Ginecologica 2010 August;62(4):293-301


language: Italian

Effects of folic acid supplementation on pregnancy outcomes: a review of randomized clinical trials

Chiaffarino F. 1, 2, Ascone G. B. 3, Bortolus R. 4, Mastroia-covo P. 5, Ricci E. 1, 2, Cipriani S. 1, 2, Parazzini F. 1, 2

1 Clinica Ostetrico Ginecologica, Università degli Studi di Milano, Fondazione IRCCS Ospedale Maggiore, Policlinico Mangiagalli, Regina Elena, Milano, Italia; 2 epi2@@4, Epidemiology Working Group Milano, Italia; 3 Direzione Generale della Prevenzione Sanitaria, Ministero del Lavoro della Salute e delle Politiche Sociali, Roma, Italia; 4 Azienda Ospedaliera Istituti Ospitalieri di Verona, Verona, Italia; 5 Alessandra Lisi International Centre on Birth Defects, ICBD, Roma, Italia


Despite the causal association between defects of the metabolism of the folate (hyperhomocysteinemia) and risk of neural tube defects are both well documented, the association between folate deficiency and other pregnancy pathologies is still not entirely clear. The present article aims to gather the data published about the relationship between serum folate and pregnancy pathologies, distinguishing between the evidences emerged from the observational studies and the results of the clinical trials. We carried out a brief examination of the relationships between folate metabolism and homocysteine. Observational studies have suggested that a good level of folate in pregnancy is associated with higher birthweight, increased placental weight and fewer preterm birth. These results were not entirely consistent with findings from clinical trials. We have identified 12 randomized clinical studies with folate supplementation versus placebo. In the clinical studies where folic acid (FA) could improve pregnancy outcomes, its effect was not statistically significant, except for three studies where FA showed a significant decrease of low birthweight. With regard to preterm birth, pre-eclampsia and abruptio placentae, although in some observational studies AF was found to be associated with a reduction of these adverse outcomes, in currently available controlled clinical trials, FA supplementation had no statistically significant effects.

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