Effects of Prenatal Fish-Oil and 5-methyltetrahydrofolate Supplementation on Cognitive Development of Children at 6.5 Y of Age

Am J Clin Nutr. 2011 Dec;94(6 Suppl):1880S-1888S. doi: 10.3945/ajcn.110.001107. Epub 2011 Aug 17.


Background: The influence of prenatal long-chain polyunsaturated fatty acids (LC-PUFAs) and folate on neurologic development remains controversial.

Objective: The objective was to assess the long-term effects of n-3 (omega-3) LC-PUFA supplementation, 5-methyltetrahydrofolate (5-MTHF) supplementation, or both in pregnant women on cognitive development of offspring at 6.5 y of age.

Design: This was a follow-up study of the NUHEAL (Nutraceuticals for a Healthier Life) cohort. Healthy pregnant women in 3 European centers were randomly assigned to 4 intervention groups. From the 20th week of pregnancy until delivery, they received a daily supplement of 500 mg docosahexaenoic acid (DHA) + 150 mg eicosapentaenoic acid [fish oil (FO)], 400 μg 5-MTHF, or both or a placebo. Infants received formula containing 0.5% DHA and 0.4% arachidonic acid (AA) if they were born to mothers receiving FO supplements or were virtually free of DHA and AA until the age of 6 mo if they belonged to the groups that were not supplemented with FO. Fatty acids and folate concentrations were determined in maternal blood at weeks 20 and 30 of pregnancy, at delivery, and in cord blood. Cognitive function was assessed at 6.5 y of age with the Kaufman Assessment Battery for Children (K-ABC).

Results: We observed no significant differences in K-ABC scores between intervention groups. Higher DHA in maternal erythrocytes at delivery was associated with a Mental Processing Composite Score higher than the 50th percentile in the offspring.

Conclusion: We observed no significant effect of supplementation on the cognitive function of children, but maternal DHA status may be related to later cognitive function in children. This trial was registered at clinicaltrials.gov as NCT01180933.

Publication types

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

MeSH terms

  • Arachidonic Acid / administration & dosage
  • Arachidonic Acid / blood
  • Child
  • Child Development / physiology*
  • Cognition / physiology*
  • Cohort Studies
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / blood
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / blood
  • Female
  • Fish Oils / administration & dosage*
  • Folic Acid / blood
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant Nutritional Physiological Phenomena
  • Male
  • Maternal Nutritional Physiological Phenomena
  • Pregnancy
  • Pregnancy Trimester, Third
  • Tetrahydrofolates / administration & dosage*


  • Fish Oils
  • Tetrahydrofolates
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Folic Acid
  • Eicosapentaenoic Acid
  • 5-methyltetrahydrofolate

Associated data

  • ClinicalTrials.gov/NCT01180933