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 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 systematic ally review r and omized 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 effect of docosahexaenoic acid and folic acid supplementation on placental apoptosis and proliferation.
The hypothesis was tested that the additional dietary uptake of n-3 fatty acids , in particular of DHA and 5-methyltetrahydrofolate ( 5-MTHF ) , during the second half of pregnancy would influence proliferation and apoptosis in the full-term human placenta . The diets of pregnant women from Spain ( n 55 ) were supplemented with modified fish oil and /or 5-MTHF or placebo , and assigned in a r and om , double-blind manner to one of the four groups . Immunohistochemistry and immunoblotting were used to detect placental proliferation and apoptosis with monoclonal antibodies for key proteins that reflected the extent of both processes : proliferation cell nuclear antigen ( PCNA ) , p53 , cytokeratin 18 neoepitope . The PCNA level in the fish oil/5-MTHF-treated group was higher by 66 % ( P < 0.05 ) than that of the placebo group , whereas the levels of p53 and cytokeratin 18 neoepitope were unaffected by treatment . PCNA expression was altered only in the trophoblast compartment ( placebo 11.1 ( se 0.5 ) % v. combination 21.5 ( se 1.2 ) % ; P < 0.05 ) , whereas the proportion of nuclei stained in endothelial and other stromal cells was similar in the placebo and combined treatment groups . No correlation was found between fish oil or 5-MTHF supplementation and the levels of the proteins . The present data suggest that supplementation with fish oil and /or 5-MTHF had no effect on the parameters reflecting placental proliferation and apoptosis . A defined combination of DHA and 5-MTHF may , however , affect placental proliferation
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 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 systematic ally review r and omized 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 .