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Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation

Katalin Fekete1*, Cristiana Berti2, Monica Trovato2, Szimonetta Lohner3, Carla Dullemeijer4, Olga W Souverein4, Irene Cetin2 and Tamás Decsi3

Author affiliations

1 Department of Biochemistry and Medical Chemistry, University of Pécs, Szigeti út 12, H-7624, Pécs, Hungary

2 Unit of Obstetrics and Gynecology and Center for Fetal Research Giorgio Pardi, University of Milan, Milan, Italy

3 Department of Paediatrics, University of Pécs, Pécs, Hungary

4 Division of Human Nutrition, Wageningen University and Research Centre, Wageningen, The Netherlands

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Citation and License

Nutrition Journal 2012, 11:75  doi:10.1186/1475-2891-11-75

Published: 19 September 2012


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 ( <a onClick="popup('','MathML',630,470);return false;" target="_blank" href="">View MathML</a>) by using random-effects meta-analysis on a loge-loge 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 <a onClick="popup('','MathML',630,470);return false;" target="_blank" href="">View MathML</a> 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.

Folate/folic acid; Pregnancy; Birth weight; Placental weight; Length of gestation; EURRECA