title: Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, Szigeti út 12, H-7624, Pécs, Hungary. katalin.fekete@kk.pte.hu
authors.forename: Katalin
authors.initials: K
authors.lastname: Fekete
authors.forename: Cristiana
authors.initials: C
authors.lastname: Berti
authors.forename: Monica
authors.initials: M
authors.lastname: Trovato
authors.forename: Szimonetta
authors.initials: S
authors.lastname: Lohner
authors.forename: Carla
authors.initials: C
authors.lastname: Dullemeijer
authors.forename: Olga W
authors.initials: OW
authors.lastname: Souverein
authors.forename: Irene
authors.initials: I
authors.lastname: Cetin
authors.forename: Tamás
authors.initials: T
authors.lastname: Decsi
mesh_terms: D001724:Birth Weight; D004032:Diet / Q000009:adverse effects; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007752:Obstetric Labor, Premature / Q000517:prevention & control; D009929:Organ Size; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000178:diet therapy / Q000517:prevention & control*; D011255:Pregnancy Maintenance; D011256:Pregnancy Outcome; D016032:Randomized Controlled Trials as Topic
chemical_list: D005492:Folic Acid