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

Systematic review and meta-analysis of randomized controlled trials in healthy pregnant women from Europe, South America, Asia, and Africa. The review assessed folate supplementation and total folate intake in relation to birth weight, placental weight, and length of gestation.

Folate supplementation during pregnancy was evaluated across randomized trials using folic acid or 5-MTHF, with doses ranging from 250 μg/day to 5 mg/day. Intervention durations ranged from 12 to 24 weeks, and total folate intake in the active arms varied accordingly.

Higher folate intake was associated with higher birth weight, showing a dose-response relationship. The pooled estimate for birth weight was significant overall (β = 0.03; 95% CI: 0.01, 0.05; P=0.001). There was no clear evidence of an effect on placental weight (β = 0.04; 95% CI: 0.00, 0.09; P=0.08) or length of gestation (β = 0.00; 95% CI: -0.01, 0.01; P=0.77). Overall, the review supports a beneficial association between folate intake during pregnancy and birth weight.

The evidence base was limited by a paucity of well-conducted randomized trials and a high risk of bias in included studies. Intervention durations and folate doses varied across trials, and the review found no clear benefit for placental weight or gestation length. Generalizability is limited to healthy pregnant women in the included settings, and adverse events were not reported.