Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants

J Pediatr. 2004 Apr;144(4):471-9. doi: 10.1016/j.jpeds.2004.01.034.


Objective: To test the efficacy and safety of long-chain polyunsaturated fatty acid (LCPUFA) supplementation with gamma-linolenic acid, a precursor of arachidonic acid, and docosahexaenoic acid in preterm infants.

Study design: Preterm (<35 weeks, < or =2000 g birth weight) infants (n=238) randomly assigned to unsupplemented or LCPUFA-supplemented formula to 9 months after term. The main outcome measure was the Bayley Mental and Psychomotor Indexes (MDI, PDI) at 18 months after term. Safety outcome measures were anthropometry (9 and 18 months), feed tolerance, infection, and clinical complications.

Results: There were no significant differences in neurodevelopment between groups overall. In preplanned subgroup analyses, LCPUFA-supplemented boys had significantly higher Bayley MDI than did control boys (difference, 5.7 points; 95% CI, 0.3 to 11.1; P=.04). LCPUFA-supplemented infants showed significantly greater weight gain (difference, 310 g; 95% CI, 30 to 590 g; P=.03) and length gain (difference, 1.0 cm; 95% CI, 0.02 to 1.9; P=.05) between birth and 9 months, with greater effect in boys (weight difference at 9 months, 510 g; 95% CI, 80 to 930 g; P=.02; length difference at 18 months, 1.8 cm; 95% CI, 0.1 to 1.8; P=.03).

Conclusions: This trial, using the strategy of providing gamma-linolenic acid as a source of arachidonic acid, showed efficacy for growth and for neurodevelopment in boys, with no adverse effects. These data have important implications for LCPUFA-supplementation strategy in preterm infants.

Publication types

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

MeSH terms

  • Body Height / physiology
  • Cognition / physiology
  • Docosahexaenoic Acids / administration & dosage*
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage*
  • Female
  • Humans
  • Infant
  • Infant Formula / chemistry*
  • Infant Nutritional Physiological Phenomena / physiology
  • Infant, Newborn
  • Infant, Premature*
  • Male
  • Milk, Human
  • Psychomotor Performance / physiology
  • Sex Factors
  • Weight Gain
  • gamma-Linolenic Acid / administration & dosage*


  • Docosahexaenoic Acids
  • gamma-Linolenic Acid
  • Eicosapentaenoic Acid