Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial

Am J Clin Nutr. 2007 May;85(5):1392-400. doi: 10.1093/ajcn/85.5.1392.


Background: Pregnant women usually meet their increased energy needs but do not always meet their increased micronutrient requirements. The supply of both folic acid and docosahexaenoic acid (DHA) has been related to positive pregnancy and infant outcomes.

Objective: We aimed to assess whether fish-oil (FO) supplementation with or without folate from gestation week 22 to birth improves maternal and fetal n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) status.

Design: We conducted a multicenter (Germany, Hungary, and Spain), randomized, double-blind, 2 x 2 factorial, placebo-controlled trial. From gestation week 22 until delivery, 311 pregnant women received daily a preparation with FO [0.5 g DHA and 0.15 g eicosapentaenoic acid (EPA)], 400 microg methyltetrahydrofolic acid (MTHF), FO with MTHF, or placebo. Outcome measures included maternal and cord plasma DHA and EPA contents at gestation weeks 20 and 30 and at delivery, indicators of pregnancy outcome, and fetal development.

Results: FO significantly (P<0.001) increased maternal DHA and EPA (% by wt), as shown by 3-factor repeated-measures ANOVA (ie, MTHF, FO, and time) with adjustment for maternal baseline DHA and EPA. In addition, FO significantly (P<0.001) increased cord blood DHA (% by wt; 2-factor ANOVA). MTHF was significantly (P=0.046) associated with increased maternal DHA (% by wt). There was no FO x MTHF interaction for the time course of DHA or EPA (P=0.927 and 0.893). Pregnancy outcomes and fetal development did not differ significantly among the intervention groups.

Conclusions: FO supplementation from gestation week 22 until delivery improves fetal n-3 LC-PUFA status and attenuates depletion of maternal stores. MTHF may further enhance maternal n-3 LC-PUFA proportions.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Dietary Supplements
  • Docosahexaenoic Acids / blood
  • Double-Blind Method
  • Eicosapentaenoic Acid / blood
  • Fatty Acids, Omega-3 / blood*
  • Female
  • Fetal Blood / chemistry*
  • Fetal Development / drug effects*
  • Fish Oils* / administration & dosage
  • Fish Oils* / chemistry
  • Folic Acid / administration & dosage*
  • Folic Acid / analogs & derivatives
  • Folic Acid / blood
  • Humans
  • Maternal Nutritional Physiological Phenomena
  • Maternal-Fetal Exchange
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Vitamin B Complex / administration & dosage*


  • Fatty Acids, Omega-3
  • Fish Oils
  • Vitamin B Complex
  • Docosahexaenoic Acids
  • 5,11-methenyltetrahydrohomofolate
  • Folic Acid
  • Eicosapentaenoic Acid